Basic and clinical aspects of gene therapy for retinopathy induced by diabetes

Current Gene Therapy

Volumn 6, Issue 2, 2006, Pages 193-214

  Ting, Julia Ho Yee ^a   Martin, Donald Keith ^a  

^a UNIVERSITY OF TECHNOLOGY SYDNEY   (Australia)

Author keywords

Health economics; Iontophoresis; Liposome; Microvasculature; Nanoparticle; Pericyte; Retina; Viral vector

Indexed keywords

ADVANCED GLYCATION END PRODUCT; ALDEHYDE REDUCTASE; ANGIOPOIETIN 1; ANGIOPOIETIN 2; CASPASE 3; CATALASE; FIDARESTAT; GLUTATHIONE PEROXIDASE; HEME OXYGENASE 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; LIPOSOME; MACROGOL; METALLOPROTEINASE; NANOPARTICLE; NITRIC OXIDE SYNTHASE; PEPTIDE DERIVATIVE; PIGMENT EPITHELIUM DERIVED FACTOR; PLASMID DNA; PLATELET DERIVED GROWTH FACTOR; POLYMER; POLYOL; PRISTINAMYCIN; PROTEIN BAX; RAPAMYCIN; SOMATOMEDIN C; SUPEROXIDE DISMUTASE; TETRACYCLINE; TRANSFORMING GROWTH FACTOR BETA1; UNINDEXED DRUG; VASCULOTROPIN; VIRUS VECTOR;

BLINDNESS; BLOOD RETINA BARRIER; CELL SURVIVAL; DIABETES MELLITUS; DIABETIC RETINOPATHY; DRUG DELIVERY SYSTEM; GENE DELIVERY SYSTEM; GENE EXPRESSION; GENE THERAPY; GENE VECTOR; GENETIC REGULATION; GENETIC TRANSFECTION; HEALTH CARE COST; HEALTH CARE SYSTEM; HEALTH ECONOMICS; HUMAN; IMMUNE RESPONSE; IONTOPHORESIS; MEDICAL RESEARCH; MICROVASCULARIZATION; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; OXIDATIVE STRESS; QUALITY OF LIFE; RETINA CELL; RETINA NEOVASCULARIZATION; REVIEW; SOCIAL ASPECT; SOCIETY; SUICIDE GENE THERAPY; SYSTEMIC CIRCULATION; VIRAL GENE DELIVERY SYSTEM; VISUAL ACUITY;

DIABETIC RETINOPATHY; DRUG DELIVERY SYSTEMS; GENE THERAPY; HUMANS;

EID: 33646246183     PISSN: 15665232     EISSN: None     Source Type: Journal    
DOI: 10.2174/156652306776359487     Document Type: Review

References (297)

1. Abe, A., Miyanohara, A. and Friedmann, T. (1998). Enhanced Gene Transfer with Fusogenic Liposomes Containing Vesicular Stomatitis Virus G Glycoprotein. J. Virol. 72(7): 6159-6163.
2. Abraham, N. G., Rezzani, R., Rodella, L., Kruger, A., Taller, D., Li Volti, G., Goodman, A. I. and Kappas, A. (2004). Overexpression of Human Heme Oxygenase-1 Attenuates Endothelial Cell Sloughing in Experimental Diabetes. Amer. J. Physiol. - Heart Circulat. Physiol. 287(6): H2468-H2477.
3. Acosta, J., Hettinga, J., Fluckiger, R., Krumrei, N., Goldfine, A., Angarita, L. and Halperin, J. (2000). Molecular Basis for a Link between Complement and the Vascular Complications of Diabetes. Proc. Natl. Acad. Sci. USA 97(10): 5450-5455.
4. Agha-Mohammadi, S. and Lotze, M. T. (2000). Regulatable Systems: Applications in Gene Ther. and Replicating Viruses. J. Clin. Invest. 105(9): 1177-1183.
5. Aiello, L., Bursell, S., Clermont, A., Duh, E., Ishii, H., Takagi, C., Mori, F., Ciulla, T., Ways, K., Jirousek, M., Smith, L. and King, G. (1997). Vascular Endothelial Growth Factor-Induced Retinal Permeability Is Medicated by Protein Kinase C in vivo and Suppressed by an Orally Effective Beta-Isoform-Selective Inhibitor. Diabetes 46(9): 1473-1480.
6. Aiello, L., Pierce, E., Foley, E., Takagi, H., Chen, H., Riddle, L., Ferrara, N., King, G. and Smith, L. (1995). Suppression of Retinal Neovascularization in vivo by Inhibition of Vascular Endothelial Growth Factor (VEGF) Using Soluble VEGF-Receptor Chimeric Proteins. Proc. Natl. Acad. Sci. USA 92(23): 10457-10461.
7. Aiello, L. P., Avery, R. L., Arrigg, P. G., Keyt, B. A., Jampel, H. D., Shah, S. T., Pasquale, L. R., Thieme, H., Iwamoto, M. A., Park, J. E., Nguyen, H. V., Aiello, L. M., Ferrara, N. and King, G. L. (1994). Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders. New England J. Med. 331(22): 1480-1487.
8. Aiello, L. P., Robinson, G., Lin, Y., Nishio, Y. and King, G. (1994). Identification of Multiple Genes in Bovine Retinal Pericytes Altered by Exposure to Elevated Levels of Glucose by Using Mrna Differential Display. Proc. Natl. Acad. Sci. USA 91: 6231-6235.
9. Akerman, M. E., Chan, W. C. W., Laakkonen, P., Bhatia, S. N. and Ruoslahti, E. (2002). Nanocrystal Targeting in vivo. Proc. Natl. Acad. Sci. USA 99(20): 12617-12621.
10. Akiyama, H., Tanaka, T., Itakura, H., Kanai, H., Maeno, T., Doi, H., Yamazaki, M., Takahashi, K., Kimura, Y., Kishi, S. and Kurabayashi, M. (2004). Inhibition of Ocular Angiogenesis by an Adenovirus Carrying the Human Von Hippel-Lindau Tumor-Suppressor Gene in vivo. Investigat. Ophthalmol. & Vis. Sci. 45(5): 1289-1296.
11. Amano, S., Yamagishi, S.-i., Kato, N., Inagaki, Y., Okamoto, T., Makino, M., Taniko, K., Hirooka, H., Jomori, T. and Takeuchi, M. (2002). Sorbitol Dehydrogenase Overexpression Potentiate Glucose Toxicity to Cultured Retinal Pericytes. Biochem. Biophys. Res. Communicat. 299(2): 183-188.
12. Anderson, W. F. (1998). Human Gene Ther. Nature 392(6679): 25-30.
13. Ando, S., Putnam, D., Pack, D. W. and Langer, R. (2000). Plga Microspheres Containing Plasmid DNA: Preservation of Supercoiled DNA Via Cryopreparation and Carbohydrate Stabilization. J. Pharmaceut. Sci. 88(1): 126-130.
14. Andrawiss, M., Maron, A., Beltran, W., Opolon, P., Connault, E., Griscelli, F., Yeh, P., Perricaudet, M. and Devauchelle, P. (2001). Adenovirus-Mediated Gene Transfer in Canine Eyes: A Preclinical Study for Gene Ther. of Human Uveal Melanoma. J. Gene Med. 3(3): 228-239.
15. Antonetti, D., Barber, A., Khin, S., Lieth, E., Tarbell, J. and Gardner, T. (1998). Vascular Permeability in Experimental Diabetes Is Associated with Reduced Endothelial Occludin Content: Vascular Endothelial Growth Factor Decreases Occludin in Retinal Endothelial Cells. Diabetes 47(12): 1953-1959.
16. Apte, R. S., Barreiro, R. A., Duh, E., Volpert, O. and Ferguson, T. A. (2004). Stimulation of Neovascularization by the Anti-Angiogenic Factor Pedf. Investigative Ophthalmology & Vis. Sci. 45(12): 4491-4497.
17. Asakawa, H., Tokunaga, K. and Kawakami, F. (2000). Elevation of Fibrinogen and Thrombin-Antithrombin Iii Complex Levels of Type 2 Diabetes Mellitus Patients with Retinopathy and Nephropathy. J. Diab. Complications 14(3): 121-126.
18. Auricchio, A., Behling, K. C., Maguire, A. M., O'Connor, E. E., Bennett, J., Wilson, J. M. and Tolentino, M. J. (2002). Inhibition of Retinal Neovascularization by Intraocular Viral-Mediated Delivery of Anti-Angiogenic Agents. Mol. Ther. 6(4): 490-494.
19. Auricchio, A., Kobinger, G., Anand, V., Hildinger, M., O'Connor, E., Maguire, A. M., Wilson, J. M. and Bennett, J. (2001). Exchange of Surface Proteins Impacts on Viral Vector Cellular Specificity and Transduction Characteristics: The Retina as a Model. Hum. Mol. Genet. 10(26): 3075-3081.
20. Auricchio, A., Rivera, V. M., Clackson, T., O'Connor, E. E., Maguire, A. M., Tolentino, M. J., Bennett, J. and Wilson, J. M. (2002). Pharmacological Regulation of Protein Expression from Adeno-Associated Viral Vectors in the Eye. Mol. Ther. 6(2): 238-242.
21. Auricchio, A. and Rolling, F. (2005). Adeno-Associated Viral Vectors for Retinal Gene Transfer and Treatment of Retinal Diseases. Cur. Gene Ther. 5(3): 339-348.
22. Australian Institute of Health and Welfare (2005). Aihw National Hospital Morbidity Database.
23. Bainbridge, J., Mistry, A., De Alwis, M., Paleolog, E., Baker, A., Thrasher, A. and Ali, R. (2002). Inhibition of Retinal Neovascularisation by Gene Transfer of Soluble VEGF Receptor Sflt-1. Gene Ther. 9: 320-326.
24. Bainbridge, J., Mistry, A., Schlichtenbrede, F., Smith, A., Broderick, C., De Alwis, M., Georgiadis, A., Taylor, P., Squires, M., Sethi, C., Charteris, D., Thrasher, A., Sargan, D. and Ali, R. (2003). Stable rAAV-Mediated Transduction of Rod and Cone Photoreceptors in the Canine Retina. Gene Ther. 10: 1336-1344.
25. Balthasar, S., Michaelis, K., Dinauer, N., von Briesen, H., Kreuter, J. and Langer, K. (2005). Preparation and Characterisation of Antibody Modified Gelatin Nanoparticles as Drug Carrier System for Uptake in Lymphocytes. Biomaterials 26(15): 2723-2732.
26. Banerjee R, Tyagi P, Li S and L, H. (2004). Anisamide-Targeted Stealth Liposomes: A Potent Carrier for Targeting Doxorubicin to Human Prostate Cancer Cells. Inter. J. Cancer 112(4): 693-700.
27. Basta, G., Lazzerini, G., Massaro, M., Simoncini, T., Tanganelli, P., Fu, C., Kislinger, T., Stern, D. M., Schmidt, A. M. and De Caterina, R. (2002). Advanced Glycation End Products Activate Endothelium through Signal-Transduction Receptor Rage: A Mechanism for Amplification of Inflammatory Responses. Circulation 105(7): 816-822.
28. Behar-Cohen, F. F., El Aouni, A., Gautier, S., David, G., Davis, J., Chapon, P. and Parel, J. M. (2002). Transscleral Coulomb-Controlled Iontophoresis of Methylprednisolone into the Rabbit Eye: Influence of Duration of Treatment, Current Intensity and Drug Concentration on Ocular Tissue and Fluid Levels. Exper. Eye Res. 74(1): 51-59.
29. Bennett, J. (2003). Immune Response Following Intraocular Delivery of Recombinant Viral Vectors. Gene Ther. 10: 977-982.
30. Bennett, J., Duan, D., Engelhardt, JF. and Maguire, AM. (1997). Real-Time, Noninvasive in Vivo Assessment of Adeno-Associated Virus-Mediated Retinal Transduction. Investig. Ophthalmol. & Vis. Sci. 38(13): 2857-2863.
31. Bennett, J., Maguire, A. M., Cideciyan, A. V., Schnell, M., Glover, E., Anand, V., Aleman, T. S., Chirmule, N., Gupta, A. R., Huang, Y., Gao, G.-P., Nyberg, W. C., Tazelaar, J., Hughes, J., Wilson, J. M. and Jacobson, S. G. (1999). Stable Transgene Expression in Rod Photoreceptors after Recombinant Adeno-Associated Virus-Mediated Gene Transfer to Monkey Retina. Proc. Natl. Acad. Sci. USA 96(17): 9920-9925.
32. Berdugo, M., Valamanesh, F., Andrieu, C., Klein, C., Benezra, D., Courtois, Y. and Behar-Cohen, F. (2003). Delivery of Antisense Oligonucleotide to the Cornea by Iontophoresis. Antisen. Nucl. Acid Drug Develop. 13(2): 107-114.
33. Berdugo Polak, M., Valamanesh, F., Courtois, Y. and Behar-Cohen, F. (2003). Safe and Efficient Intracorneal Delivery of an Antisense Oligonucleotide Using Iontophoresis. Investig. Ophthalmol. & Vis. Sci. 44(5 (E-abstract)): 828-B803.
34. Bertran, J., Yang, Y., Hargrove, P., Vanin, E. F. and Nienhuis, A. W. (1998). Targeted Integration of a Recombinant Globin Gene Adeno-Associated Viral Vector into Human Chromosome 19. Ann. NY Acad. Sci. 850(1): 163-177.
35. Bessis, N., GarciaCozar, F. and Boissier, M. (2004). Immune Responses to Gene Ther. Vectors: Influence on Vector Function and Effector Mechanisms. Gene Ther. 11(Suppl. 1): S10-S17.
36. Bestman-Smith, J., Désormeaux, A., Tremblay, M. and Bergeron, M. (2000). Targeting Cell-Free Hiv and Virally-Infected Cells with Anti-Hla-Dr Immunoliposomes Ccontaining Amphotericin B. AIDS 14(16): 2457-2465.
37. Bhadra, D., Gupta, G., Bhadra, S., Umamaheshwari, R. and Jein, N. (2004). Multicomposite Ultrathin Capsules for Sustained Ocular Delivery of Ciprofloxacin Hydrochloride. J. Pharm. Pharmaceut. Sci. 7(2): 241-251.
38. Bhakta, G., Mitra, S. and Maitra, A. (2005). DNA Encapsulated Magnesium and Manganous Phosphate Nanoparticles: Potential Non-Viral Vectors for Gene Delivery. Biomaterials 26(14): 2157-2163.
39. Bierhaus, A., Illmer, T., Kasper, M., Luther, T., Quehenberger, P., Tritschler, H., Wahl, P., Ziegler, R., Muller, M. and Nawroth, P. P. (1997). Advanced Glycation End Product (Age)-Mediated Induction of Tissue Factor in Cultured Endothelial Cells Is Dependent on Rage. Circulation 96(7): 2262-2271.
40. Birch, K., Heath, W., Hermeling, R., Johnston, C., Stramm, L., Dell, C., Smith, C., Williamson, J. and Reifel-Miller, A. (1996). Ly290181, an Inhibitor of Diabetes-Induced Vascular Dysfunction, Blocks Protein Kinase C-Stimulated Transcriptional Activation through Inhibition of Transcription Factor Binding to a Phorbol Response Element. Diabetes 45(5): 642-650.
41. 2+ Signaling in Endothelial Cells. J. Cell Physiol. 193(1):80-92.
42. Bisht, S., Bhakta, G., Mitra, S. and Maitra, A. (2005). Pdna Loaded Calcium Phosphate Nanoparticles: Highly Efficient Non-Viral Vector for Gene Delivery. Internat. J. Pharmaceutics 288(1): 157-168.
43. Blau, H. M. and Rossi, F. M. V. (1999). Tet B or Not Tet B: Advances in Tetracycline-Inducible Gene Expression. Proc. Natl. Acad. Sci. USA 96(3): 797-799.
44. Bobbink, I., de Boer, H., Tekelenburg, W., Banga, J. and de Groot, P. (1997). Effect of Extracellular Matrix Glycation on Endothelial Cell Adhesion and Spreading: Involvement of Vitronectin. Diabetes 46(1): 87-93.
45. Boehm, B., Lang, G., Feldmann, B., Kurkhaus, A., Rosinger, S., Volpert, O., Lang, G. and Bouck, N. (2003). Proliferative Diabetic Retinopathy Is Associated with a Low Level of the Natural Ocular Anti-Angiogenic Agent Pigment Epithelium-Derived Factor (Pedf) in Aqueous Humor. A Pilot Study. Horm. Metabol. Res. 35(6): 382-386.
46. Boeri, D., Maiello, M. and Lorenzi, M. (2001). Increased Prevalence of Microthromboses in Retinal Capillaries of Diabetic Individuals. Diabetes 50: 1432-1439.
47. Booth, G., Stalker, T., Lefer, A. and Scalia, R. (2002). Mechanisms of Amelioration of Glucose-Induced Endothelial Dysfunction Following Inhibition of Protein Kinase C in vivo. Diabetes 51(5): 1556-1564.
48. Borras, T., Gabelt, B. T., Klintworth, G. K., Peterson, J. C. and Kaufman, P. L. (2001). Non-Invasive Observation of Repeated Adenoviral Gfp Gene Delivery to the Anterior Segment of the Monkey Eye in vivo. J. Gene Med. 3(5): 437-449.
49. Boulanger, E., Wautier, M.-P., Gane, P., Mariette, C., Devuyst, O. and Wautier, J.-L. (2004). The Triggering of Human Peritoneal Mesothelial Cell Apoptosis and Oncosis by Glucose and Glycoxydation Products. Nephrology Dialysis Transplant. 19(9): 2208-2216.
50. Boulton, M., Foreman, D., Williams, G. and McLeod, D. (1998). VEGF Localisation in Diabetic Retinopathy. Brit. J. Ophthalmol. 82(5): 561-568.
51. Brown, G., Brown, M., Sharma, S., Brown, H., Gozum, M. and Denton, P. (2000). Quality of Life Associated with Diabetes Mellitus in an Adult Population. J. Diab. Complicat. 14(1): 18-24.
52. Brown, J., Pedula, K. and Summers, K. (2003). Diabetic Retinopathy: Contemporary Prevalence in a Well-Controlled Population. Diabet. Care 26(9): 2637-2642.
53. Brown, M. M., Brown, G. C., Sharma, S. and Shah, G. (1999). Utility Values and Diabetic Retinopathy. Amer. J. Ophthalnol. 128(3): 324-330.
54. Brunner, S., Sauer, T., Carotta, S., Cotten, M., Saltik, M. and Wagner, E. (2000). Cell Cycle Dependence of Gene Transfer by Lipoplex, Polyplex and Recombinant Adenovirus. Gene Ther. 7(5): 401-407.
55. Burgos, R., Mateo, C., Canton, A., Hernandez, C., Mesa, J. and Simo, R. (2000). Vitreous Levels of Igf-1, Igf Binding Protein 1, and Igf Binding Protein 3 in Proliferative Diabetic Retinopathy. Diabet. Care 23(1): 80-83.
56. Cai, J., Ahmad, S., Jiang, W., Huang, J., Kontos, C., Boulton, M. and Ahmed, A. (2003). Activation of Vascular Endothelial Growth Factor Receptor-1 Sustains Angiogenesis and Bcl-2 Expression via the Phosphatidylinositol 3 Kinase Pathway in Endothelial Cells - Complications. Diabetes 52(12): 2959-2968.
57. Chakravarthy, U. and Gardiner, T. (1999). Endothelium-Derived Agents in Pericyte Function/Dysfunction. Prog. Retin. Eye Res. 18(4): 511-527.
58. Chaum, E. (2001). Comparative Analysis of the Uptake and Expression of Plasmid Vectors in Human Ciliary and Retinal Pigment Epithelial Cells in vitro. J. Cell. Biochemist 83(4): 671-677.
59. Chaum, E., Hatton, M. and Stein, G. (1999). Polyplex-Mediated Gene Transfer into Human Retinal Pigment Epithelial Cells in vitro. J.. Cell. Biochemist. 76(1): 153-160.
60. Chavakis, T., Cines, D. B., Rhee, J.-S., Liang, O. D., Schubert, U., Hammes, H.-P., Higazi, A. A.-R., Nawroth, P. P., Preissner, K. T. and Bdeir, K. (2004). Regulation of Neovascularization by Human Neutrophil Peptides (α-Defensins): A Link between Inflammation and Angiogenesis. Fed. Amer. Societ. Exper. Biol. Jr. 18(11): 1306-1308.
61. Chen, R., Doiron, B. and Kahn, A. (1995). Glucose Responsiveness of a Reporter Gene Transduced into Hepatocytic Cells Using a Retroviral Vector. Fed. Amer. Societ. Exper. Biol. Lett. 365(2-3): 223-226.
62. Chibber, R., Ben-Mahmud, B., Mann, G., Zhang, J. and Kohner, E. (2003). Protein Kinase C B2-Dependent Phosphorylation of Core 2 Glenac-T Promotes Leukocyte-Endothelial Cell Adhesion: A Mechanism Underlying Capillary Occlusion in Diabetic Retinopathy. Diabetes 52(6): 1519-1527.
63. Chirmule, N., Propert, K., Magosin, S., Qian, Y., Qian, R. and Wilson, J. (1999). Immune Responses to Adenovirus and Adeno-Associated Virus in Humans. Gene Ther. 6(9): 1574-1583.
64. Chu, T.-C., He, Q. and Potter, D. E. (2002). Biodegradable Calcium Phosphate Nanoparticles as a New Vehicle for Delivery of a Potential Ocular Hypotensive Agent. J. Ocular Pharmacol. Therapeut. 18(6): 507-514.
65. Clemons, K., Ranney, D. and Stevens, D. (2001). A Novel Heparin-Coated Hydrophilic Preparation of Amphotericin B Hydrosomes. Cur. Opin. Investigat. Drugs 2(4): 480-487.
66. Colin, M., Maurice, M., Trugnan, G., Kornprobst, M., Harbottle, R., Knight, A., Cooper, R., Miller, A., Capeau, J., Coutelle, C. and Brahimi-Horn, M. (2000). Cell Delivery, Intracellular Trafficking and Expression of an Integrin-Mediated Gene Transfer Vector in Tracheal Epithelial Cells. Gene Ther. 7(2): 139-152.
67. Connolly, J. (2002). Lentiviruses in Gene Ther. Clinical Res.. Gene Ther. 9(24): 1730-1734.
68. Connor, J. and Huang, L. (1985). Efficient Cytoplasmic Delivery of a Fluorescent Dye by Ph-Sensitive Immunoliposomes. J. Cell Biology 101(2): 582-589.
69. Cornelis, S., Vandenbrunden, M., Ruysschaert, J.-M. and Elouahabi, A. (2002). Role of Intracellular Cationic Liposome-DNA Complex Dissociation in Transfection Mediated by Cationic Lipids. DNA and Cell Biology 21(2): 91-97.
70. Crook, K., Stevenson, B. J., Dubouchet, M. and Porteous, D. J. (1998). Inclusion of Cholesterol in Dotap Transfection Complexes Increases the Delivery of DNA to Cells in vitro in the Presence of Serum. Gene Ther. 5(1): 137-143.
71. Dagher, Z., Park, Y. S., Asnaghi, V., Hoehn, T., Gerhardinger, C. and Lorenzi, M. (2004). Studies of Rat and Human Retinas Predict a Role for the Polyol Pathway in Human Diabetic Retinopathy. Diabetes 53(9): 2404-2411.
72. Dai, Y., Schwarz, E., Gu, D., Zhang, W., Sarvetnick, N. and Verma, I. (1995). Cellular and Humoral Immune Responses to Adenoviral Vectors Containing Factor Ix Gene: Tolerization of Factor Ix and Vector Antigens Allows for Long-Term Expression. Proc. Natl. Acad. Sci. USA 92(5): 1401-1405.
73. Davies, J., Ciavatta, V., Boatright, J. and Nickerson, J. (2003). Delivery of Several Forms of DNA, DNA-Rna Hybrids, and Dyes across Human Sclera by Electrical Fields. Mol. Vision 9: 569-578.
74. Davis, S. S. (1997). Biomedical Applications of Nanotechnology - Implications for Drug Targeting and Gene Then.. Trends in Biotechnol. 15(6): 217-224.
75. Dawson, D. W., Volpert, O. W., Gillis, P., Crawford, S. E., Xu, H.-J., Benedict, W. and Bouck, N. P. (1999). Pigment Epithielium-Derived Factor: A Potent Inhibitor of Angiogenesis. Sci. 285(5425): 245-248.
76. de Campos, A., Diebold, Y., Carvalho, E., Sanchez, A. and Alonso, M. (2004). Chitosan Nanoparticles as New Ocular Drug Delivery Systems: In Vitro Stability, in vivo Fate, and Cellular Toxicity. Pharmaceut. Res. 21(5): 803-810.
77. Dejneka, N., Auricchio, A., Maguire, A., Ye, X., Gao, G., Wilson, J. and Bennett, J. (2001). Pharmacologically Regulated Gene Expression in the Retina Following Transduction with Viral Vectors. Gene Ther. 8(6): 442-446.
78. Dejneka, N. S. and Bennett, J. (2001). Gene Ther. and Retinitis Pigmentosa: Advances and Future Challenges. BioEssays 23(7): 662-668.
79. Dezawa, M., Takano, M., Negishi, H., Mo, X., Oshitari, T. and Sawada, H. (2002). Gene Transfer into Retinal Ganglion Cells by in vivo Electroporation: A New Approach. Micron 33(1): 1-6.
80. Dharma, S., Fishman, P. and Peyman, G. (1986). A Preliminary Study of Corneal Penetration of 125i-Labelled Idoxuridine Liposome. Acta Ophthalmologica (Copenh.) 64(3): 298-301.
81. Donnelly, R., Emslie-Smith, A. M., Gardner, I. D. and Morris, A. D. (2000). Abc of Arterial and Venous Disease: Vascular Complications of Diabetes. Brit, Med. Jr. 320(7241): 1062-1066.
82. Dowty, M., Williams, P., Zhang, G., Hagstrom, J. and Wolff, J. (1995). Plasmid DNA Entry into Postmitotic Nuclei of Primary Rat Myotubes. Proc. Natl. Acad Sci. USA 92(10):4572-4576.
83. Du, Y., Sarthy, V. P. and Kern, T. S. (2004). Interaction between No and Cox Pathways in Retinal Cells Exposed to Elevated Glucose and Retina of Diabetic Rats. Amer. J. Physiol. - Regulat. Integrat. Comparat. Physiol. 287(4): R735-R741.
84. Engerman, R. and Kern, T. (1993). Aldose Reductase Inhibition Fails to Prevent Retinopathy in Diabetic and Galactosemic Dogs. Diabetes 42(6): 820-825.
85. Fanelli, A., Hadjadj, S., Gallois, Y., Fumeron, F., Betoule, D., Grandchamp, B. and Marre, M. (2002). Polymorphism of Aldose Reductase Gene and Susceptibility to Retinopathy and Nephropathy in Caucasians with Type 1 Diabetes. Archives des maladies du coeur et des vaisseaux 95(7-8): 701-708.
86. Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R., Myers, R. H., Pericak-Vance, M. A., Risch, N. and Van Duijn, C. M. (1997). Effects of Age, Sex, and Ethnicity on the Association between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-Analysis. J. Amer. Med. Associat. 278(16): 1349-1356.
87. Fennell, J., Brosnan, M., Frater, A., Hamilton, C., Alexander, M., Nicklin, S., Heistad, D., Baker, A. and Dominiczak, A. (2002). Adenovirus-Mediated Overexpression of Extracellular Superoxide Dismutase Improves Endothelial Dysfunction in a Rat Model of Hypertension. Gene Ther. 9(2): 110-117.
88. Ferris, F. (1993). How Effective Are Treatments for Diabetic Retinopathy? The J. Amer. Med. Associat. 269: 1290-1291.
89. Filion, M. C. and Phillips, N. C. (1998). Major Limitations in the Use of Cationic Liposomes for DNA Delivery. Inter. J. Pharmaceutics 162(1-2): 159-170.
90. Fink, D. J., DeLuca, N. A., Goins, W. F. and Glorioso, J. C. (1996). Gene Transfer to Neurons Using Herpes Simplex Virus-Based Vectors. Ann. Rev. NeuroSci. 19(1): 265-287.
91. Folliot, S., Briot, D., Conrath, H., Provost, N., Cherel, Y., Moullier, P. and Rolling, F. (2003). Sustained Tetracycline-Regulated Transgene Expression in vivo in Rat Retinal Ganglion Cells Using a Single Type 2 Adeno-Associated Viral Vector. J. Gene Ther. 5(6): 493-501.
92. Fong, D., Aiello, L., Ferris, F. and Klein, R. (2004). Diabetic Retinopathy. Diab. Care 27(10): 2540-2553.
93. Forbes, J. M., Yee, L. T. L., Thallas, V., Lassila, M., Candido, R., Jandeleit-Dahm, K. A., Thomas, M. C., Burns, W. C., Deemer, E. K., Thorpe, S. M., Cooper, M. E. and Allen, T. J. (2004). Advanced Glycation End Product Interventions Reduce Diabetes-Accelerated Atherosclerosis. Diabetes 53(7): 1813-1823.
94. Frank, R. (2002). Potential New Medical Therapies for Diabetic Retinopathy: Protein Kinase C Inhibitors. Amer. J. Ophthalmology 133: 693-698.
95. Frank, R., Turczyn, T. and Das, A. (1990). Pericyte Coverage of Retinal and Cerebral Capillaries. Investigative Ophthalmol. & Vis. Sci. 31(6): 999-1007.
96. Fussenegger, M. (2001). The Impact of Mammalian Gene Regulation Concepts on Functional Genomic Res., Metabolic Engineering, and Advanced Gene Therapies. Biotechnol. Prog. 17: 1-51.
97. Fussenegger, M., Morris, R. P., Fux, C., Rimann, M., Von Stockar, B., Thompson, C. J. and Bailey, J. E. (2000). Streptogramin-Based Gene Regulation Systems for Mammalian Cells. Nat. Biotechnol. 18(11): 1203-1208.
98. Gao, G., Li, Y., Zhang, D., Gee, S., Crosson, C. and Ma, J.-x. (2001). Unbalanced Expression of VEGF and Pedf in Ischemia-Induced Retinal Neovascularization. Fed. Amer. Societ. Exper. Biol. Lett. 489(2-3): 270-276.
99. Gavini, E., Chetoni, P., Cossu, M., Alvarez, M. G., Saettone, M. F. and Giunchedi, P. (2004). Plga Microspheres for the Ocular Delivery of a Peptide Drug, Vancomycin Using Emulsification/Spray-Drying as the Preparation Method: in vitro/in vivo Studies. Eur. J. Pharmaceut. and Biopharmaceut. 57(2): 207-212.
100. Gessner, A., Olbrich, C., Schroder, W., Kayser, O. and Muller, R. H. (2001). The Role of Plasma Proteins in Brain Targeting: Species Dependent Protein Adsorption Patterns on Brain-Specific Lipid Drug Conjugate (Ldc) Nanoparticles. Inter. J. Pharmaceut. 214(1-2): 87-91.
101. Giannavola, C., Bucolo, C., Maltese, A., Paolino, D., Vandelli, M., Puglisi, G., Lee, V. and M, F. (2003). Influence of Preparation Conditions on Acyclovir-Loaded Poly-D,L-Lactic Acid Nanospheres and Effect of Peg Coating on Ocular Drug Bioavailability. Pharmaceut. Res. 20(4): 584-590.
102. Glaser, B., Campochiaro, P., Davis, J. J. and Sato, M. (1985). Retinal Pigment Epithelial Cells Release an Inhibitor of Neovascularization. Archives of Opthalmol. 103(12): 1870-1875.
103. Goldman, M. and Wilson, J. (1995). Expression of Alpha V Beta 5 Integrin Is Necessary for Efficient Adenovirus-Mediated Gene Transfer in the Human Airway. J. Virol. 69(10): 5951-5958.
104. Grant, C., Ponnazhagan, S., Wang, A., Srivastava, A. and Li , T. (1997). Evaluation of Recombinant Adeno-Associated Virus as a Gene Transfer Vector for the Retina. Curr. Eye Res. 16: 949-956.
105. Gu, X., El-Remessy, A. B., Brooks, S. E., Al-Shabrawey, M., Tsai, N.-T. and Caldwell, R. B. (2003). Hyperoxia Induces Retinal Vascular Endothelial Cell Apoptosis through Formation of Peroxynitrite. Amer. J. Physiol. - Cell Physiol. 285(3): C546-C554.
106. Gupta, A. K. and Gupta, M. (2005). Cytotoxicity Suppression and Cellular Uptake Enhancement of Surface Modified Magnetic Nanoparticles. Biomaterials 26(13): 1565-1573.
107. Halhal, M., Renard, G., Courtois, Y., BenEzra, D. and Behar-Cohen, F. (2004). Iontophoresis: From the Lab to the Bed Side. Exper. Eye Res. 78(3): 751-757.
108. Hammes, H., Lin, J., Bretzel, R., Brownlee, M. and Breier, G. (1998). Upregulation of the Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptor System in Experimental Background Diabetic Retinopathy of the Rat. Diabetes 47(3): 401-406.
109. Hammes, H., Lin, J., Renner, O., Shani, M., Lundqvist, A., Betsholtz, C., Brownlee, M. and Deutsch, U. (2002). Pericytes and the Pathogenesis of Diabetic Retinopathy. Diabetes 51(10): 3107-3112.
110. Hammes, H., Weiss, A., Hess, S., Araki, N., Horiuchi, S., Brownlee, M. and Preissner, K. (1996). Modification of Vitronectin by Advanced Glycation Alters Functional Properties in vitro and in the Diabetic Retina. Laboratory Invest. 75(3): 325-338.
111. Hammes, H. P., Bartmann, A., Engel, L. and Wãlfroth, P. (1997). Anti-oxidant Treatment of Experimental Diabetic Retinopathy in Rats with Nicanartine. Diabetologia 40(6): 629-634.
112. Hangai, M., Kaneda, Y., Tanihara, H. and Honda, Y. (1996). In Vivo Gene Transfer into the Retina Mediated by a Novel Liposome System. Investigative Ophthalmology & Vis. Sci. 37(13): 2678-2685.
113. Hangai, M. Murata, T., Miyawaki, N., Spee, C., Lim, J. I., He, S., Hinton, D. R. and Ryan, S. J. (2001). Angiopoietin-1 Upregulation by Vascular Endothelial Growth Factor in Human Retinal Pigment Epithelial Cells. Investig. Ophthalmol. Vis. Sci. 42(7): 1617-1625.
114. Hartnett, M., Stratton, R., Browne, R., Rosner, B., Lanham, R. and Armstrong, D. (2000). Serum Markers of Oxidative Stress and Severity of Diabetic Retinopathy. Diab. Care 23: 234-340.
115. Harui, A., Suzuki, S., Kochanek, S. and Mitani, K. (1999). Frequency and Stability of Chromosomal Integration of Adenovirus Vectors. J. Virol. 73(7): 6141-6146.
116. Healthcare Cost and Utilization Project (HCUP) (2002). National and Regional Estimates on Hospital Use for All Patients from the HCUP Nationwide Inpatient Sample (NIS) Database.
117. Hellstrom, A., Perruzzi, C., Ju, M., Engstrom, E., Hard, A.-L., Liu, J.-L., Albertsson-Wikland, K., Carlsson, B., Niklasson, A., Sjodell, L., LeRoith, D., Senger, D. R. and Smith, L. E. H. (2001). Low Igf-I Suppresses VEGF-Survival Signaling in Retinal Endothelial Cells: Direct Correlation with Clinical Retinopathy of Prematurity. Proc. Natl Acad. Sci. USA 98(10): 5804-5808.
118. Hellstrom, M., Gerhardt, H., Kalen, M., Li, X., Eriksson, U., Wolburg, H. and Betsholtz, C. (2001). Lack of Pericytes Leads to Endothelial Hyperplasia and Abnormal Vascular Morphogenesis. J. Cell Biology 153(3): 543-554.
119. Himmelstein, K., Guvenir, I. and Patton, T. (1978). Preliminary Pharmacokinetic Model of Pilocarpine Uptake and Distribution in the Eye. J. Pharmaceut. Sci. 67(5): 603-606.
120. Hirko, A., Tang, F. and Hughes, J. A. (2003). Cationic; Lipid Vectors for Plasmid DNA Delivery. Curr. Med. Chem. 10(14): 1185-1193.
121. Hofman, P., Blaauwgeers, H. G. T., Vrensen, G. F. J. M. and Schlingemann, R. O. (2001). Role of VEGF-a in Endothelial Phenotypic Shift in Human Diabetic Retinopathy and VEGF-a-Induced Retinopathy in Monkeys. Ophthalmic Res. 33(3): 156-162.
122. Horwath-Winter, J., Schmut, O., Haller-Schober, E.-M., Gruber, A. and Rieger, G. (2005). Iodide Iontophoresis as a Treatment for Dry Eye Syndrome. Brit. J. Ophthalmol. 89(1): 40-44.
123. Igarashi, T., Miyake, K., Kato, K., Watanabe, A., Ishizaki, M., Ohara, K. and Shimada, T. (2003). Lentivirus-Mediated Expression of Angiostatin Efficiently Inhibits Neovascularization in Murine Proliferative Retinopathy Model. Gene Ther. 10: 219-226.
124. Ikuno, Y. and Kazlauskas, A. (1999). Recent Progress in Gene Ther. for Eye Diseases. Gene Ther. Mol. Biol. 4: 203-208.
125. Illum L, Church AE, Butterworth MD, Arien A, Whetstone J and SS, D. (2001). Development of Systems for Targeting the Regional Lymph Nodes for Diagnostic Imaging: In vivo Behaviour of Colloidal Peg-Coated Magnetite Nanospheres in the Rat Following Interstitial Administration. Pharmaceut. Res. 18(5): 640-645.
126. Ishikawa, H., Takano, M., Matsumoto, N., Sawada, H., Ide, C., Mimura, O. and Dezawa, M. (2005). Effect of Gdnf Gene Transfer into Axotomized Retinal Ganglion Cells Using in vivo Electroporation with a Contact Lens-Type Electrode. Gene Ther. 12(4): 289-298.
127. Jiang, L., Rampalli, S., George, D., Press, C., Bremer, E., O'Gorman, M. and Bohn, M. (2004). Tight Regulation from a Single Tet-Off rAAV Vector as Demonstrated by Flow Cytometry and Quantitative, Real-Time Pcr. Gene Ther. 11(13): 1057-1067.
128. Jo, N., Ogata, N., Aoki, M., Otsuji, T., Morishita, R., Kaneda, Y. and Matsumura, M. (2002). Effective Transfection of a Cis Element "Decoy" of the Nuclear Factor-Kappab Binding Site into the Experimental Choroidal Neovascularization. Curr. Eye Res. 24(6): 465-473.
129. Johnson, P., Miyanohara, A., Levine, F., Cahill, T. and Friedmann, T. (1992). Cytotoxicity of a Replication-Defective Mutant of Herpes Simplex Virus Type 1. J. Virol. 66(5): 2952-2965.
130. Jones, D., Clegg, J. and Farrar, G. (1998). Oral Delivery of Micro-Encapsulated DNA Vaccines. Devel. Biolog. Standardization (Basel). 92: 149-155.
131. Joussen, A., Poulaki, V., Ly Le, M., Koizumi, K., Esser, C., Janicki, H., Schraermeyer, U., Kociok, N., Fauser, S., Kirchhof, B., Kern, T. and Adamis, A. (2004). A Central Role for Inflammation in the Pathogenesis of Diabetic Retinopathy. Fed. Amer. Societ. Exper. Biol. Jr. 18: 1450-1452.
132. Joussen, A. M., Poulaki, V., Tsujikawa, A., Qin, W., Qaum, T., Xu, Q., Moromizato, Y., Bursell, S.-E., Wiegand, S. J., Rudge, J., Ioffe, E., Yancopoulos, G. D. and Adamis, A. P. (2002). Suppression of Diabetic Retinopathy with Angiopoietin-1. Amer. J. Pathology 160(5): 1683-1693.
133. Kao, Y.-L., Donaghue, K., Chan, A., Knight, J. and Silink, M. (1999). An Aldose Reductase Intragenic Polymorphism Associated with Diabetic Retinopathy. Diab. Res. and Clin. Practice 46(2): 155-160.
134. Kato, N., Yashima, S., Suzuki, T., Nakayama, Y. and Jomori, T. (2003). Long-Term Treatment with Fidarestat Suppresses the Development of Diabetic Retinopathy in Stz-Induced Diabetic Rats. J. Diab. Complications 17(6): 374-379.
135. Kempen, J., O'Colmain, B., Leske, M., Haffner, S., Klein, R., Moss, S., Taylor, H. and Hamman, R. (2004). The Prevalence of Diabetic Retinopathy among Adults in the United States. Archives of Ophthalmology 122(4): 552.
136. Kent, M., Light, N. and Bailey, A. (1985). Evidence for Glucose-Mediated Covalent Cross-Linking of Collagen after Glycosylation in vitro. Biochem. Jr. 25(3): 745-752.
137. Kem, T. and Engerman, R. (1995). Galactose-Induced Retinal Microangiopathy in Rats. Investigat. Ophthalmol. Vis. Sci. 36(2): 490-496.
138. Khoobehi, B., Peyman, G., Niesman, M. and Oncel, M. (1989). Hyperthermia and Temperature-Sensitive Liposomes: Selective Delivery of Drugs into the Eye. Japanese J. Ophthalmology 33(4): 405-412.
139. Kimura, H., Sakamoto, T., Cardillo, J., Spee, C., Hinton, D., Gordon, E., Anderson, W. and Ryan, S. (1996). Retrovirus-Mediated Suicide Gene Transduction in the Vitreous Cavity of the Eye: Feasibility in Prevention of Proliferative Vitreoretinopathy. Hum. Gene Ther. 7(7): 799-808.
140. Kitchell, J. P. and Wise, D. L. (1985). Poly(Lactic/Glycolic Acid) Biodegradable Drug-Polymer Matrix Systems. Meth. in Enzymol. 112: 436-448.
141. Klein, R. (2004). Is Intensive Management of Blood Pressure to Prevent Vis. Loss in Persons with Type 2 Diabetes Indicated? Archives of Ophthalmol. 122(11): 1707-1709.
142. Klein, R., Klein, B., Moss, S., Wong, T., Hubbard, L., Cruickshanks, K. and Palta, M. (2004). The Relation of Retinal Vessel Caliber to the Incidence and Progression of Diabetic Retinopathy: Xix: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Archives of Ophthal. 122(1): 76.
143. Klein, R., Klein, B. E. K., Moss, S. E., DeMets, D.L., Kaufman, I, Voss, P.S. (1984). Prevalence of Diabetes Mellitus in Southern Wisconsin. Amer. J. Epidemiol. 119(1): 54-61.
144. Knott, R., Robertson, M. and Forrester, J. (1993). Regulation of Glucose Transporter (Glut 3) and Aldose Reductase Mma Inbovine Retinal Endothelial Cells and Retinal Pericytes in High Glucose and High Galactose Culture. Diabetologia 36(9): 808-812.
145. Kocur, I. and Resnikoff, S. (2002). Vis. Impairment and Blindness in Europe and Their Prevention. Brit. J. Ophthalmol. 86(7): 716-722.
146. Kowluru, R., Tang, J. and Kern, T. (2001). Abnormalities of Retinal Metabolism in Diabetes and Experimental Galactosemia: Vii. Effect of Long-Term Administration of Antioxidants on the Development of Retinopathy. Diabetes 50(8): 1938.
147. Kralinger, M. T., Voigt, M., Kieselbach, G. F., Hamasaki, D., Hayden, B. C. and Parel, J.-M. (2003). Ocular Delivery of Acetylsalicylic Acid by Repetitive Coulomb-Controlled Iontophoresis. Ophthalmic Res. 35(2): 102.
148. Kwon, O. J., Brautbar, C., Weintrob, N., Sprecher, E., Saphirman, C., Bloch, K., Pinhas-Hamiel, O., Assah, S., Vardi, P. and Israel, S. (2001). ImmunoGenet. of Hla Class Ii in Israeli Ashkenazi Jewish,
149. Labat-Moleur, F., Steffan, A., Brisson, C., Perron, H., Feugeas, O., Furstenberger, P., Oberling, F., Brambilla, E. and Behr, J. (1996). An Electron Microscopy Study into the Mechanism of Gene Transfer with Lipopolyamines. Gene Ther. 3(11): 1010-1017.
150. Lamoureux, E., Hassell, J. and Keeffe, J. (2004). The Impact of Diabetic Retinopathy on Participation in Daily Living. Archives of Ophthalmology 122(1): 84-88.
151. Lassila, M., Seah, K. K., Allen, T. J., Thallas, V., Thomas, M. C., Candido, R., Burns, W. C., Forbes, J. M., Calkin, A. C., Cooper, M. E. and Jandeleit-Dahm, K. A. M. (2004). Accelerated Nephropathy in Diabetic Apolipoprotein E-Knockout Mouse: Role of Advanced Glycation End Products. J. Amer. Soc. Nephrol. 15(8): 2125-2138.
152. Lebherz, C., Auricchio, A., Maguire, A. M., Rivera, V. M., Tang, W., Grant, R. L., Clackson, T., Bennett, J. and Wilson, J. M. (2005). Long-Term Inducible Gene Expression in the Eye via Adeno-Associated Virus Gene Transfer in Nonhuman Primates. Hum. Gene Ther. 16(2): 178-186.
153. Lechardeur, D. and Lukacs, G. (2002). Intracellular Barriers to Non-Viral Gene Transfer. Curr. Gene Ther. 2(2): 183-194.
154. Lechardeur, D., Sohn, K., Haardt, M., Joshi, P., Monck, M., Graham, R., Beatty, B., Squire, J., O'Brodovich, H. and Lukacs, G. (1999). Metabolic Instability of Plasmid DNA in the Cytosol: A Potential Barrier to Gene Transfer. Gene Ther. 6(4): 482-497.
155. Lee, E. R., Marshall, J., Siegel, C. S., Jiang, C., Yew, N. S., Nichols, M. R., Nietupski, J. B., Ziegler, R. J., Lane, M. B., Wang, K. X., Wan, N. C., Scheule, R. K., Harris, D. J., Smith, A. E. and Cheng, S. H. (1996) Detailed Analysis of Structures and Formulations of Cationic Lipids for Efficient Gene Transfer to the Lung. Hum. Gene Ther. 7(14): 1701-1717.
156. Lee, V. and Robinson, J. (1986). Topical Ocular Drug Delivery: Recent Developments and Future Challenges. J. Ocular Pharmacol. 2(1): 67-108.
157. Lehrman, S. (1999). Virus Treatment Questioned after Gene Ther. Death. Nature 401(6753): 517-518.
158. Lewis, J. G., Lin, K.-Y., Kothavale, A., Flanagan, W. M., Matteucci, M. D., DePrince, R. B., Mook, Jr. R. A., Hendren, R. W. and Wagner, R. W. (1996). A Serum-Resistant Cytofectin for Cellular Delivery of Antisense Oligodeoxynucleotides and Plasmid DNA. Proc. Natl. Acad. Sci. USA 93(8): 3176-3181.
159. Li, L., Sawamura, T. and Renier, G. (2003). Glucose Enhances Endothelial Lox-1 Expression: Role for Lox-1 in Glucose-Induced Human Monocyte Adhesion to Endothelium. Diabetes 52(7): 1843-1850.
160. Li, S., Tseng, W., Stolz, D., Wu, S., Watkins, S. and Huang, L. (1999). Dynamic Changes in the Characteristics of Cationic Lipidic Vectors after Exposure to Mouse Serum: Implications for Intravenous Lipofection. Gene Ther. 6(4): 585-594.
161. Li, W., Liu, X., Yanoff, M., Cohen, S. and Ye, X. (1996). Cultured Retinal Capillary Pericytes Die by Apoptosis after an Abrupt Fluctuation from High to Low Glucose Levels: A Comparative Study with Retinal Capillary Endothelial Cells. Diabetologia 39(5): 537-547.
162. Li, W., Yanoff, M., Jian, B. and He, Z. (1999). Altered Mrna Levels of Antioxidant Enzymes in Pre-Apoptotic Pericytes from Human Diabetic Retinas. Cell Mol. Biology 45(1): 59-66.
163. Li, W., Yanoff, M., Liu, X. and Ye, X. (1997). Retinal Capillary Pericyte Apoptosis in Early Human Diabetic Retinopathy. Chinese Med. Jr. 110(9): 659-663.
164. Liang, F.-Q., Aleman, T. S., Dejneka, N. S., Dudus, L., Fisher, K. J., Maguire, A. M., Jacobson, S. G. and Bennett, J. (2001). Long-Term Protection of Retinal Structure but Not Function Using rAAV.Cntf in Animal Models of Retinitis Pigmentosa. Mol. Ther. 4(5): 461-472.
165. Lim, S. C., Caballero, A. E., Smakowshi, P., LoGerfo, F. W., Horton, E. S. and Veves, A. (1999). Soluble Intercellular Adhesion Molecule, Vascular Cell Adhesion Molecule, and Impaired Microvascular Reactivity Are Early Markers of Vasculopathy in Type 2 Diabetic Individuals without Microalbuminuria. Diabetes Care 22(11): 1865-1870.
166. Liu, X. Y., Brandt, C. R., Gabelt, B. T., Bryar, P. J., Smith, M. E. and Kaufman, P. L. (1999). Herpes Simplex Virus Mediated Gene Transfer to Primate Ocular Tissues. Exper. Eye Res. 69(4): 385-395.
167. Loewen, N., Fautsch, M. P., Teo, W. L., Bahler, C. K., Johnson, D. H. and Poeschla, E. M. (2004). Long-Term, Targeted Genetic Modification of the Aqueous Humor Outflow Tract Coupled with Non-Invasive Imaging of Gene Expression in vivo. Investigat. Ophthalmol. Vis. Sci. 45(9): 3091-3098.
168. Lopes de Menezes DE, Pilarski LM and TM, A. (1998). In vitro and in vivo Targeting of Immunoliposomal Doxorubicin to Human B-Cell Lymphoma. Cancer Res. 58(15): 3320-3330.
169. Lorenzi, M. and Gerhardinger, C. (2001). Early Cellular and Molecular Changes Induced by Diabetes in the Retina. Diabetologia 44: 791-804.
170. Lu, L., Garcia, C. A. and Mikos, A. G. (1999). In vitro Degradation of Thin Poly(Dl-Lactic-Co-Glycolic Acid) Films. J. Biomed. Materials Res. 46(2): 236-244.
171. Lundstrom, K. (2004). Gene Ther. Applications of Viral Vectors. Technology in Cancer Res. Treat. 3(5): 467-477.
172. MacDonald, R. C., Ashley, G. W., Shida, M. M., Rakhmanova, V. A., Tarahovsky, Y. S., Pantazatos, D. P., Kennedy, M. T., Pozharski, E. V., Baker, K. A., Jones, R. D., Rosenzweig, H. S., Choi, K. L., Qiu, R. and McIntosh, T. J. (1999). Physical and Biological Properties of Cationic Triesters of Phosphatidylcholine. Biophys. Jr. 77(5): 2612-2629.
173. Maitani Y, Kawano K, Yamada K, Nagai T and K, T. (2001). Efficiency of Liposomes Surface-Modified with Soybean-Derived Sterylglucoside as a Liver Targeting Carrier in Hepg2 Cells. J. Control Rel. 75(3): 381-389.
174. Mallam, J. N., Hurwitz, M. Y., Mahoney, T., Chevez-Barrios, P. and Hurwitz, R. L. (2004). Efficient Gene Transfer into Retinal Cells Using Adenoviral Vectors: Dependence on Receptor Expression. Investigat. Ophthalmol. Vis. Sci. 45(6): 1680-1687.
175. Marty C and RA, S. (2005). Cytotoxic Tumor Targeting with Scfv Antibody-Modified Liposomes. Methods in Mol. Med. 109: 389-402.
176. McGee Sanftner, L. H., Rendahl, K. G., Quiroz, D., Coyne, M., Ladner, M., Manning, W. C. and Flannery, J. G. (2001). Recombinant Aav-Mediated Delivery of a Tet-Inducible Reporter Gene to the Rat Retina. Mol. Ther. 3(5): 688-696.
177. Meneses, P., Hajjar, K., Berns, K. and Duvoisin, R. (2001). Recombinant Angiostatin Prevents Retinal Neovascularization in a Murine Proliferative Retinopathy Model. Gene Ther. 8: 646-648.
178. Miller, D. G., Adam, M. A. and Miller, A. D. (1990). Gene Transfer by Retrovirus Vectors Occurs Only in Cells That Are Actively Replicating at the Time of Infection. Mol. Cellul. Biology 10(8): 4239-4242.
179. Miller, J., Adamis, A., Shima, D., D'Amore, P., Moulton, R., O'Reilly, M., Folkman, J., Dvorak, H., Brown, L. and Berse, B. (1994). Vascular Endothelial Growth Factor/Vascular Permeability Factor Is Temporally and Spatially Correlated with Ocular Angiogenesis in a Primate Model. Amer. J. Pathology 145(3): 574-584.
180. Miyamoto, K., Khosrof, S., Bursell, S., Rohan, R., Murata, T., Clermont, A., Aiello, L. P., Ogura, Y. and Adamis, A. P. (1999). Prevention of Leukostasis and Vascular Leakage in Streptozotocin-Induced Diabetic Retinopathy Via Intercellular Adhesion Molecule-1 Inhibition. Proc. Natl. Acad. Sci. USA 96: 10836-10841.
181. Mori, K., Gehlbach, P., Ando, A., McVey, D., Wei, L. and Campochiaro, P. A. (2002). Regression of Ocular Neovascularization in Response to Increased Expression of Pigment Epithelium-Derived Factor. Investigative Ophthalmol, Vis. Sci. 43(7): 2428-2434.
182. Mori, K., Gehlbach, P., Yamamoto, S., Duh, E., Zack, D. J., Li, Q., Berns, K. I., Raisler, B. J., Hauswirth, W. W. and Campochiaro, P. A. (2002). Aav-Mediated Gene Transfer of Pigment Epithelium-Derived Factor Inhibits Choroidal Neovascularization. Investigat. Ophthalmol. Vis. Sci. 43(6): 1994-2000.
183. Murata, M. (2000). Genetic Polymorphisms Associated with Thrombotic Disorders in the Japanese Population. Fibrinolysis and Proteolysis 14(2-3): 155-164.
184. Murata, T., Hoffmann, S., Ishibashi, T., Spee, C., Gordon, E. M., Anderson, W. F., Hinton, D. R. and Ryan, S. J. (1998). Retrovirus-Mediated Gene Transfer Targeted to Retinal Photocoagulation Sites. Diabetologia 41(5): 500-506.
185. Nambu, H., Nambu, R., Oshima, Y., Hackett, S., Okoye, G., Wiegand, S., Yancopoulos, G., Zack, D. and Campochiaro, P. (2004). Angiopoietin 1 Inhibits Ocular Neovascularization and Breakdown of the Blood-Retinal Barrier. Gene Ther. 11: 865-873.
186. Nambu, H., Umeda, N., Kachi, S., Oshima, Y., Akiyama, H., Nambu, R. and Campochiaro, P. (2005). Angiopoietin 1 Prevents Retinal Detachment in an Aggressive Model of Proliferative Retinopathy, but Has No Effect on Established Neovascularization. J. Cell Physiol. 204(1): 227-235.
187. Newmeyer, D. and Forbes, D. (1988). Nuclear Import Can Be Separated into Distinct Steps in vitro: Nuclear Pore Binding and Translocation. Cell 52(5): 641-653.
188. Newmeyer, D., Lucocq, J., Burglin, T. and De Robertis, E. (1986). Assembly in vitro of Nuclei Active in Nuclear Protein Transport: ATP Is Required for Nucleoplasmin Accumulation. Eur. Mol. Biol. Organiz. Jr. 5(3): 501-510.
189. Ng, Y. C., Jacobs, P. and Johnson, J. A. (2001). Productivity Losses Associated with Diabetes in the U.S. Diab. Care 24(2): 257-261.
190. Nicklin, S. A., Buening, H., Dishart, K. L., de Alwis, M., Girod, A., Hacker, U., Thrasher, A. J., Ali, R. R., Hallek, M. and Baker, A. H. (2001). Efficient and Selective Aav2-Mediated Gene Transfer Directed to Human Vascular Endothelial Cells. Mol. Ther. 4(3): 174-181.
191. Niesman, M., Khoobehi, B. and Peyman, G. (1992). Encapsulation of Sodium Fluorescein for Dye Release Studies. Investigat. Ophthalmol. Vis. Sci. 33(7): 2113-2119.
192. Noisakran, S. and Carr, D. (2000). Therapeutic Efficacy of DNA Encoding Ifn-Alpha1 against Corneal Hsv-1 Infection. Curr. Eye Res. 20(5): 405-412.
193. Obrosova, I., Minchenko, A., Vasupuram, R., White, L., Abatan, O., Kumagai, A., Frank, R. and Stevens, M. (2003). Aldose Reductase Inhibitor Fidarestat Prevents Retinal Oxidative Stress and Vascular Endothelial Growth Factor Overexpression in Streptozotocin-Diabetic Rats. Diabetes 52(3): 864-871.
194. Ogura, Y., Guran, T., Shahidi, M., Mori, M. and Zeimer, R. (1991). Feasibility of Targeted Drug Delivery to Selective Areas of the Retina. Investigative Ophthalmol. Vis. Sci. 32(8): 2351-2356.
195. Ohno-Matsui, K., Hirose, A., Yamamoto, S., Saikia, J., Okamoto, N., Gehlbach, P., Duh, E. J., Hackett, S., Chang, M., Bok, D., Zack, D. J. and Campochiaro, P. A. (2002). Inducible Expression of Vascular Endothelial Growth Factor in Adult Mice Causes Severe Proliferative Retinopathy and Retinal Detachment. Amer. J. Pathology 160(2): 711-719.
196. Olivier, J.-C. (2005). Drug Transport to Brain with Targeted Nanoparticles. NeuroRx 2(1): 108-119.
197. Oshima, Y., Shukunami, C., Honda, J., Nishida, K., Tashiro, F., Miyazaki, J.-i., Hiraki, Y. and Tano, Y. (2003). Expression and Localization of Tenomodulin, a Transmembrane Type Chondromodulin-I-Related Angiogenesis Inhibitor, in Mouse Eyes. Investigative Ophthalmol. Vis. Sci. 44(5): 1814-1823.
198. Otsubo, T., Maruyama, K., Maesaki, S., Miyazaki, Y., Tanaka, E., Takizawa, T., Moribe, K., Tomono, K., Tashiro, T. and Kohno, S. (1998). Long-Circulating Immunoliposomal Amphotericin B against Invasive Pulmonary Aspergillosis in Mice. Antimicrobial. Agents and Chemother. 42(1): 40-44.
199. Ovchinnikov, I., Illarioshkin, S., Bagyeva, G., Miklina, N. and Ivanova-Smolenskaya, I. (1997). Repeat Expansion and Phenotypic Variability of Friedreich's Ataxia in Families of Different Ethnic Origin from European-Asian Region. Neuromusc. Disord. 7(6-7): 457.
200. Palmer, T. D., Rosman, G. J., Osborne, W. R. A. and Miller, A. D. (1991). Genetically Modified Skin Fibroblasts Persist Long after Transplantation but Gradually Inactivate Introduced Genes. Proc. Natl. Acad. Sci. USA 88: 1330-1334.
201. Pang, C., Baum, L. and Lam, D. (2000). Hunting for Disease Genes in Multi-Functional Diseases. Clin. Chem. Lab. Med. 38(9): 819-825.
202. Park, J., Takahara, N., Gabriele, A., Chou, E., Naruse, K., Suzuma, K., Yamauchi, T., Ha, S., Meier, M., Rhodes, C. and King, G. (2000). Induction of Endothelin-1 Expression by Glucose: An Effect of Protein Kinase C Activation. Diabetes 49(7): 1239-1248.
203. Park, Y. S., Kim, N. H. and Jo, I. (2003). Hypoxia and Vascular Endothelial Growth Factor Acutely up-Regulate Angiopoietin-1 and Tie2 Mrna in Bovine Retinal Pericytes. Microvas. Res. 65(2): 125-131.
204. Phillips, M., del Rio, I. and Quiroz, H. (1994). Opportunities for Cost Reduction in Diabetic Retinopathy Treatment: Case Study from Mexico. Bulletin of the Pan Amer. Health Organizat. 28(1): 50-61.
205. Pierce, E., Avery, R., Foley, E., Aiello, L. and Smith, L. (1995). Vascular Endothelial Growth Factor/Vascular Permeability Factor Expression in a Mouse Model of Retinal Neovascularization. Proc. Natl. Acad. Sci. USA 92(3): 905-909.
206. Podesta, F., Romeo, G., Liu, W., Krajewski, S., Reed, J., Gerhardinger, C. and Lorenzi, M. (2000). Bax Is Increased in the Retina of Diabetic Subjects and Is Associated with Pericyte Apoptosis in vivo and in vitro. American J. Pathology 156(3): 1025-1032.
207. Poulaki, V., Joussen, A. M., Mitsiades, N., Mitsiades, C. S., Iliaki, E. F. and Adamis, A. P. (2004). Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy. Amer. J. Pathology 165(2): 457-469.
208. Punglia, R., Lu, M., Hsu, J., Kuroki, M., Tolentino, M., Keough, K., Levy, A., Levy, N., Goldberg, M., D'Amato, R. and Adamis, A. (1997). Regulation of Vascular Endothelial Growth Factor Expression by Insulin-Like Growth Factor 1. Diabetes 46(10): 1619-1626.
209. Qaddoumi, M., Gukasyan, H., Davda, J., Labhasetwar, V., Kim, K. and Lee, V. (2003). Clathrin and Caveolin-1 Expression in Primary Pigmented Rabbit Conjunctival Epithelial Cells: Role in Plga Nanoparticle Endocytosis. Mol. Vision 9: 559-568.
210. Quagliaro, L., Piconi, L., Assaloni, R., Martinelli, L., Motz, E. and Ceriello, A. (2003). Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells: The Role of Protein Kinase C and NAD(P)H-Oxidase Activation. Diabetes 52(11): 2795-2804.
211. Radwan Almofti, M., Harashima, H., Shinohara, Y., Almofti, A., Baba, Y. and Kiwada, H. (2003). Cationic Liposome-Mediated Gene Delivery: Biophysical Study and Mechanism of Internalization. Archives of Biochem. and Biophys. 410(2): 246-253.
212. Rahmani, B., Tielsch, J., Katz, J., Gottsch, J., Quigley, H., Javitt, J. and Sommer, A. (1996). The Cause-Specific Prevalence of Vis. Impairment in an Urban Population. The Baltimore Eye Survey. Ophthalmol. 103(11): 1721-1726.
213. Raisler, B. J., Berns, K. I., Grant, M. B., Beliaev, D. and Hauswirth, W. W. (2002). Adeno-Associated Virus Type-2 Expression of Pigmented Epithelium-Derived Factor or Kringles 1-3 of Angiostatin Reduce Retinal Neovascularization. Proc. Natl. Acad. Sci. USA 99(13): 8909-8914.
214. Rakoczy, P., Brankov, M., Fonceca, A., Zaknich, T., Rae, B. and Lai, C. (2003). Enhanced Recombinant Adeno-Associated Virus-Mediated Vascular Endothelial Growth Factor Expression in the Adult Mouse Retina: A Potential Model for Diabetic Retinopathy. Diabetes 52(3): 857-863.
215. Rang, A. and Will, H. (2000). The Tetracycline-Responsive Promoter Contains Functional Interferon-Inducible Response Elements. Nucl. Acids Res. 28(5): 1120-1125.
216. Ray, D., Mishra, M., Ralph, S., Read, I., Davies, R. and Brenchley, P. (2004). Association of the VEGF Gene with Proliferative Diabetic Retinopathy but Not Proteinuria in Diabetes. Diabetes 53(3): 861-864.
217. Reich, S. and Bennett, J. (2003). Gene Ther. for Ocular Neovascularisation: A Cure in Sight. Curr. Opin. Genet. Develop. 13: 317-322.
218. Reiser, K. M. (1998). Nonenzymatic Glycation of Collagen in Aging and Diabetes. Proc. Soc. Exper. Biol. Med. 218(1): 23-37.
219. Rensen PC, Sliedregt LA, Ferns M, Kieviet E, van Rossenberg SM, van Leeuwen SH, van Berkel TJ and EA., B. (2001). Determination of the Upper Size Limit for Uptake and Processing of Ligands by the Asialoglycoprotein Receptor on Hepatocytes in vitro and in vivo. J. Biolog. Chemist. 276(40): 37577-37584.
220. Resnikoffl, S., PascoliniII, D., Etya'aleIII, D., KocurIII, I., Pararajasegaram, R., PokharelIII, G. P. and MariottiIII, S. P. (2004). Global Data on Vis. Impairment in the Year 2002. Bull. World Health Organisation 82(11): 844-851.
221. Richardson, W., Mills, A., Dilworth S., Laskey, R. and Dingwall, C. (1988). Nuclear Protein Migration Involves Two Steps: Rapid Binding at the Nuclear Envelope Followed by Slower Translocation through Nuclear Pores. Cell 52(5): 655-664.
222. Risau, W. (1991). Induction of Blood-Brain Barrier Endothelial Cell Differentiation. Annals of the New York Academy of Sci. 633: 405-419.
223. Robison, W. J., Nagata, M., Tillis, T., Laver, N. and Kinoshita, J. (1989). Aldose Reductase and Pericyte-Endothelial Cell Contacts in Retina and Optic Nerve. Investigat. Ophthalmol. Vis. Sci. 30(11): 2293-2299.
224. Romeo, G., Liu, W., Asnaghi, V., Kern, T. and Lorenzi, M. (2002). Activation of Nuclear Factor-Kappab Induced by Diabetes and High Glucose Regulates a Proapoptotic Program in Retinal Pericytes. Diabetes 51(7): 2241-2248.
225. Rota, R., Riccioni, T., Zaccarini, M., Lamartina, S., Gallo, A., Fusco, A., Kovesdi, I., Balestrazzi, E., Abeni, D. and Ali, R. C., MC (2004). Marked Inhibition of Retinal Neovascularization in Rats Following Soluble-Fit-1 Gene Transfer. J. Gene Med. 6(9): 992-1002.
226. Roy, I., Mitra, S., Maitra, A. and Mozumdar, S. (2003). Calcium Phosphate Nanoparticles as Novel Non-Viral Vectors for Targeted Gene Delivery. Internat. J. Pharmaceut. 250(1): 25-33.
227. Roy, I., Ohulchanskyy, T. Y., Bharali, D. J., Pudavar, H. E., Mistretta, R. A., Kaur, N. and Prasad, P. N. (2005). Optical Tracking of Organically Modified Silica Nanoparticles as DNA Carriers: A Nonviral, NanoMed. Approach for Gene Delivery. Proc. Natl. Acad. Sci. USA 102(2): 279-284.
228. Ruberte, J., Ayuso, E., Navarro, M., Carretero, A., Nacher, V., Haurigot, V., George, M., Llombart, C., Casellas, A., Costa, C., Bosch, A. and Bosch, F. (2004). Increased Ocular Levels of Igf-1 in Transgenic Mice Lead to Diabetes-Like Eye Disease. J. Clin. Invest. 113(8): 1149-1157.
229. Sang Yoo, H., Eun Lee, J., Chung, H., Chan Kwon, I. and Young Jeong, S. (2005). Self-Assembled Nanoparticles Containing Hydrophobically Modified Glycol Chitosan for Gene Delivery. J. Control. Rel. 103(1): 235-243.
230. Sapra, P. and Allen, T. M. (2004). Improved Outcome When B-Cell Lymphoma Is Treated with Combinations of Immunoliposomal Anticancer Drugs Targeted to Both the Cd19 and Cd20 Epitopes. Clin. Cancer Res. 10(7): 2530-2537.
231. Sato, S., Secchi, E., Lizak, M., Fukase, S., Ohta, N., Murata, M., Tsai, J. and Kador, P. (1999). Polyol Formation and Nadph-Dependent Reductases in Dog Retinal Capillary Pericytes and Endothelial Cells. Investigat. Ophthal. Vis. Sci. 40(3): 697-704.
232. Schaffer, D. V., Fidelman, N. A., Dan, N. and Lauffenburger, D. A. (2000). Vector Unpacking as a Potential Barrier for Receptor-Mediated Polyplex Gene Delivery. Biotechnol. Bioengineer. 67(5): 598-606.
233. Schiffelers RM, Molema G, ten Hagen TL, Janssen AP, Schraa AJ, Kok RJ, Koning GA and G, S. (2002). Ligand-Targeted Liposomes Directed against Pathological Vasculature. J. Liposome Res. 12(1-2): 129-135.
234. Scott, I. U., Schein, O. D., Feuer, W. J., Folstein, M. F. and Bandeen-Roche, K. (2001). Emotional Distress in Patients with Retinal Disease. American J. Ophthalmol. 131(5): 584-589.
235. Sharma, S., Brown, G., Brown, M., Shah, G., Snow, K., Brown, H. and Hollands, H. (2000). Converting Vis. Acuity to Utilities. Canadian J. Ophthalmol. 35(3): 267-272.
236. Sharma, S., Hollands, H., Brown, G., Brown, M., Shah, G. and Sharma, S. (2001). The Cost-Effectiveness of Early Vitrectomy for the Treatment of Vitreous Hemorrhage in Diabetic Retinopathy. Curr. Opin. Ophthalmol. 12(3): 230-234.
237. Shen, W.-Y., Lai, C.-M., Lai, Y. K. Y., Zhang, D., Zaknich, T., Sutanto, E. N., Constable, I. J. and Rakoczy, P. E. (2003). Practical Considerations of Recombinant Adeno-Associated Virus-Mediated Gene Transfer for Treatment of Retinal Degenerations. The J. Gene Med. 5(7): 576-587.
238. Shenawy, F. E., Refall, M. R., Abbas, F., Mosaad, Y., Nafls, A. R. E. and Nabi, A. (1996). DQ Polymorphism in Juvenile Onset Diabetes Mellitus. Hum. Immunol. 47(1-2): 156.
239. Shih, S.-C., Ju, M., Liu, N., Mo, J.-R., Ney, J. J. and Smith, L. E. H. (2003). Transforming Growth Factor B1 Induction of Vascular Endothelial Growth Factor Receptor 1: Mechanism of Pericyte-Induced Vascular Survival in vivo. Proc. Natl. Acad. Sci. USA 100(26): 15859-15864.
240. Sieczkiewicz, G. J. and Herman, I. M. (2003). Tgf-B1 Signalling Controls Retinal Pericyte Contractile Protein Expression. Microvas. Res. 66(3): 190-196.
241. Simoes, S., Slepushkin, V., Duzgunes, N. and Pedroso de Lima, M. C. (2001). On the Mechanisms of Internalization and Intracellular Delivery Mediated by Ph-Sensitive Liposomes. Biochimica et Biophysica Acta (BBA) - Biomembranes 1515(1): 23-37.
242. Sjolie, A. and Moller, F. (2004). Medical Management of Diabetic Retinopathy. Diab. Med. 21: 667-672.
243. Slepushkin, V. A., Simoes, S., Dazin, P., Newman, M. S., Guo, L. S. and de Lima, M. C. P. (1997). Sterically Stabilized Ph-Sensitive Liposomes: Intracellular Delivery of Aqueous Contents and Prolonged Circulation in vivo. J. Biol. Chem. 272(4): 2382-2388.
244. Smith, L. E. H., Shen, W., Perruzzi, C., Soker, S., Kinose, F., Xu, X., Robinson, G., Driver, S., Bischoff, J., Zhang, B., Schaeffer, J. M. and Senger, D. R. (1999). Regulation of Vascular Endothelial Growth Factor-Dependent Retinal Neovascularization by Insulin-Like Growth Factor-1 Receptor. Nat. Med. 5(12): 1390-1395.
245. Spencer, B., Agarwala, S., Miskulin, M., Smith, M. and Brandt, C. R. (2000). Herpes Simplex Virus-Mediated Gene Delivery to the Rodent Vis. System. Investig. Ophthalmol. Vis. Sci. 41(6): 1392-1401.
246. Spranger, J., Osterhoff, M., Reimann, M., Mohlig, M., Ristow, M., Francis, M. K., Cristofalo, V., Hammes, H.-P., Smith, G., Boulton, M. and Pfeiffer, A. F. H. (2001). Loss of the Anti-Angiogenic Pigment Epithelium-Derived Factor in Patients with Angiogenic Eye Disease. Diabetes 50(12): 2641-2645.
247. St. Louis, D. and Verma, I. M. (1988). An Alternative Approach to Somatic Cell Gene Ther.. Proc. Nat. Acad. Sci. USA 85: 3150-3154.
248. Stefansson, E., Hatchell, D., Fisher, B., Sutherland, F. and Machemer, R. (1986). Panretinal Photocoagulation and Retinal Oxygenation in Normal and Diabetic Cats. Amer. J. Ophthalmol. 101(6): 657-664.
249. Stitt, A., Gardiner, T. A., Anderson, N. L., Canning, P., Frizzell, N., Duffy, N., Boyle, C., Januszewski, A. S., Chachich, M., Baynes, J. W. and Thorpe, S. R. (2002). The Age Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes. Diabetes 51(9): 2826-2832.
250. Stone, J., Chan-Ling, T., Pe'er, J., Itin, A., Gnessin, H. and Keshet, E. (1996). Roles of Vascular Endothelial Growth Factor and Astrocyte Degeneration in the Genesis of Retinopathy of Prematurity. Investigat. Ophthalmol. Vis. Sci. 37(2): 290-299.
251. Straubinger, R., Duzgunes, N. and Papahadjopoulos, D. (1985). Ph-Sensitive Liposomes Mediate Cytoplasmic Delivery of Encapsulated Macromolecules. Fed. Amer. Societ. Exper. Biol. Letts. 179(1): 148-154.
252. Sulochana, K. N., Ramakrishnan, S., Rajesh, M., Coral, K. and Badrinath, S. S. (2001). Diabetic Retinopathy: Molecular Mechanisms, Present Regime of Treatment and Future Perspectives. Curr. Sci. 80(2): 133-142.
253. Sun, L., Li, J. and Xiao, X. (2000). Overcoming Adeno-Associated Virus Vector Size Limitation through Viral DNA Heterodimerization. Nat. Med. 6(5): 599-602.
254. Suzuma, K., Takahara, N., Suzuma, I., Isshiki, K., Ueki, K., Leitges, M., Aiello, L. P. and King, G. L. (2002). Characterization of Protein Kinase C B Isoform's Action on Retinoblastoma Protein Phosphorylation, Vascular Endothelial Growth Factor-Induced Endothelial Cell Proliferation, and Retinal Neovascularization. Proc. Natl. Acad. Sci. USA 99(2): 721-726.
255. Takagi, H., King, G. and Aiello, L. (1998). Hypoxia Upregulates Glucose Transport Activity through an Adenosine-Mediated Increase of Glutl Expression in Retinal Capillary Endothelial Cells. Diabetes 47(9): 1480-1488.
256. Talcott, B. and Moore, M. S. (1999). Getting across the Nuclear Pore Complex. Trends in Cell Biol. 9(8): 312-318.
257. Tamarat, R., Silvestre, J.-S., Huijberts, M., Benessiano, J., Ebrahimian, T. G., Duriez, M., Wautier, M.-P., Wautier, J. L. and Levy, B. I. (2003). Blockade of Advanced Glycation End-Product Formation Restores Ischemia-Induced Angiogenesis in Diabetic Mice. Proc. Natl. Acad. Sci. USA 100(14): 8555-8560.
258. Taverna, M. J., Sola, A., Guyot-Argenton, C., Pacher, N., Bruzzo, F., Chevalier, A., Slama, G., Reach, G. and Selam, J. L. (2002). Enos4 Polymorphism of the Endothelial Nitric Oxide Synthase Predicts Risk for Severe Diabetic Retinopathy. Diab. Med. 19(3): 240-245.
259. Templeton, N. S. (2003). Cationic Liposomes as in vivo Delivery Vehicles. Curr. Med. Chem. 10(14): 1279-1287.
260. Treins, C., Giorgetti-Peraldi, S., Murdaca, J. and Van Obberghen, E. (2001). Regulation of Vascular Endothelial Growth Factor Expression by Advanced Glycation End Products. J. Biol. Chem. 276(47): 43836-43841.
261. Tros de Ilarduya, C. and Duzgunes, N. (2000). Efficient Gene Transfer by Transferrin Lipoplexes in the Presence of Serum. Biochimica et Biophysica Acta (BBA) - Biomembranes 1463(2): 333-342.
262. Tsukamoto, K., Smith, P., Glick, J. M. and Rader, D. J. (1997). Liver-Directed Gene Transfer and Prolonged Expression of Three Major Human Apoe Isoforms in Apoe-Deficient Mice. J. Clin. Invest. 100(1): 107-114.
263. UK Department of Health (2005). Hospital Episode Statistics Database.
264. Van Bambeke, F., Kerkhofs, A., Schanck, A., Remacle, C., Sonveaux, E., Tulkens, P. and Mingeot-Leclercq, M. (2000). Biophysical Studies and Intracellular Destabilization of Ph-Sensitive Liposomes. Lipid 35(2): 213-223.
265. Verma, I. M. and Somia, N. (1997). Gene Ther. - Promises, Problems and Prospects. Nature 389(6648): 239-242.
266. Vitiello, L., Chonn, A., Wasserman, J. D., Duff, C. and Worton, R. G. (1996). Condensation of Plasmid DNA with Polylysine Improves Liposome-Mediated Gene Transfer into Established and Primary Muscle Cells. Gene Ther. 3(5): 396-404.
267. Voigt, M., Kralinger, M., Kieselbach, G., Chapon, P., Anagnoste, S., Hayden, B. and Parel, J.-M. (2002). Ocular Aspirin Distribution: A Comparison of Intravenous, Topical, and Coulomb-Controlled Iontophoresis Administration. Investigat. Ophthalmol. Vis. Sci. 43(10): 3299-3306.
268. Walter, E., Moelling, K., Pavlovic, J. and Merkle, H. P. (1999). Microencapsulation of DNA Using Poly(-Lactide-Co-Glycolide): Stability Issues and Release Characteristics. J. Controlled Rel. 61(3): 361-374.
269. Wang, A., Nomura, M., Patan, S. and Ware, J. A. (2002). Inhibition of Protein Kinase Cα Prevents Endothelial Cell Migration and Vascular Tube Formation in vitro and Myocardial Neovascularization in vivo. Circul. Res. 90(5): 609-616.
270. Wautier, J. (1986). Role of Erythrocytes in Thromboembolism Pathology. Annales de Medecine Interne (Paris) 137(6): 477-479.
271. Wautier, J. and Guillausseau, P. (1998). Diabetes, Advanced Glycation Endproducts and Vascular Disease. Vas. Med. 3(2): 131-137.
272. Wautier, J., Paton, R., Wautier, M., Pintigny, D., Abadie, E., Passa, P. and Caen, J. (1981). Increased Adhesion of Erythrocytes to Endothelial Cells in Diabetes Mellitus and Its Relation to Vascular Complications. N. Engl. J. Med. 305(5): 237-242.
273. Wautier, J., Wautier, M., Schmidt, A., Anderson, G., Hori, O., Zoukourian, C., Capron, L., Chappey, O., Yan, S., Guillausseau, P. and Stern, D. (1994). Advanced Glycation End Products (Ages) on the Surface of Diabetic Erythrocytes Bind to the Vessel Wall Via a Specific Receptor Inducing Oxidant Stress in the Vasculature: A Link between Surface-Associated Ages and Diabetic Complications. Proc. Natl. Acad. Sci. USA 91(16): 7742-7746.
274. Wautier, J.-L., Zoukourian, C., Chappey, O., Wautier, M.-P., Guillausseau, P.-J., Cao, R., Hori, O., Stern, D. and Schmidt, A. M. (1996). Receptor-Mediated Endothelial Cell Dysfunction in Diabetic Vasculopathy. Soluble Receptor for Advanced Glycation End Products Blocks Hyper-permeability in Diabetic Rats. J. Clin. Invest. 97(1): 238-243.
275. Weber, M., Rabinowitz, J., Provost, N., Conrath, H., Folliot, S., Briot, D., Cherel, Y., Chenuaud, P., Samulski, J., Moullier, P. and Rolling, F. (2003). Recombinant Adeno-Associated Virus Serotype 4 Mediates Unique and Exclusive Long-Term Transduction of Retinal Pigmented Epithelium in Rat, Dog, and Nonhuman Primate after Subretinal Delivery. Mol. Ther. 7(6): 774-781.
276. Weill, D., Wautier, J., Dosquet, C., Wautier, M., Carreno, M. and Boval, B. (1995). Monocyte Modulation of Endothelial Leukocyte Adhesion Molecules. J. Lab. Clin. Med. 125(6): 768-774.
277. Weiter, J. and Zuckerman, R. (1980). The Influence of the Photoreceptor-Rpe Complex on the Inner Retina. An Explanation for the Beneficial Effects of Photocoagulation. Ophthalmology 87(11): 1133-1139.
278. Wen, Y., Skidmore, J. C., Porter-Turner, M. M., Rea, C. A., Khokher, M. A. and Singh, B. M. (2002). Relationship of Glycation, Antioxidant Status and Oxidative Stress to Vascular Endothelial Damage in Diabetes. Diabetes, Obesity and Metab. 4(5): 305-308.
279. Wiley Clinical Trial Database (2005). Vectors Used in Gene Ther. Clinical Trial. Gene Ther. Clin. Trial Worldwide, J. Gene Med. 2005:
280. Woodcock, A., Bradley, C., Plowright, R., ffytche, T., Kennedy-Martin, T. and Hirsch, A. (2004). The Influence of Diabetic Retinopathy on Quality of Life: Interviews to Guide the Design of a Condition-Specific, Individualised Questionnaire: The Retdqol. Patient Education and Counseling 53(3): 365-383.
281. World Health Organisation (2002). Diabetes Mellitus. World Health Organisation Fact Sheet No138.
282. Wu, W., Lai, C., Chen, S., Sun, M., Xiao, X., Chen, T., Tsai, R., Kuo, S. and Tsao, Y. (2004). Gdnf Gene Ther. Attenuates Retinal Ischemic Injuries in Rats. Mol. Vis. 10: 93-102.
283. Xu, X., Li, Z., Luo, D., Huang, Y., Zhu, J., Wang, X., Hu, H. and Patrick, C. P. (2002). Exogenous Advanced Glycosylation End Products Induce Diabetes-Like Vascular Dysfunction in Normal Rats: A Factor in Diabetic Retinopathy. Graefes Archives of Clin. Exper. Ophthalmol. 241(1): 56-62.
284. Yamagishi, S.-i., Amano, S., Inagaki, Y., Okamoto, T., Koga, K., Sasaki, N., Yamamoto, H., Takeuchi, M. and Makita, Z. (2002). Advanced Glycation End Products-Induced Apoptosis and Overexpression of Vascular Endothelial Growth Factor in Bovine Retinal Pericytes. Biochem. Biophys. Res. Communicat. 290(3): 973-978.
285. Yamagishi, S.-i., Inagaki, Y., Amano, S., Okamoto, T., Takeuchi, M. and Makita, Z. (2002). Pigment Epithelium-Derived Factor Protects Cultured Retinal Pericytes from Advanced Glycation End Product-Induced Injury through Its Anti-Oxidative Properties. Biochem. Biophys. Res. Communicat. 296(4): 877-882.
286. Yamagishi, S.-I., Yonekura, H., Yamamoto, Y., Katsuno, K., Sato, F., Mita, I., Ooka, H., Satozawa, N., Kawakami, T., Nomura, M. and Yamamoto, H. (1997). Advanced Glycation End Products-Driven Angiogenesis in vitro. Induction of the Growth and Tube Formation of Human Microvascular Endothelial Cells through Autocrine Vascular Endothelial Growth Factor. J. Biol. Chemist. 272(13): 8723-8730.
287. Yang, L., Quan, S. and Abraham, N. G. (1999). Retrovirus-Mediated Ho Gene Transfer into Endothelial Cells Protects against Oxidant-Induced Injury. Amer. J. Physiol. - Lung Cellular and Mol. Physiol. 277(1): L127-L133.
288. Yang, Y., Ertl, H. C. J. and Wilson, J. M. (1994). Mhc Class I-Cestricted Cytotoxic T Lymphocytes to Viral Antigens Destroy Hepatocytes in Mice Infected with El-Deleted Recombinant Adenoviruses. Immunity 1(5): 433-442.
289. Ye, X., Rivera, V. M., Zoltick, P. Jr. F. C., Schnell, M. A., Gao, G.-p., Hughes, J. V., Gilman, M. and Wilson, J. M. (2004). Regulated Delivery of Therapeutic Proteins after in vivo Somatic Cell Gene Transfer. Sci. 283(5398): 88-91.
290. Yi, Q., Bamroongsuk, P., McCarthy, D. J., Mukesh, B. N. and Harper, C. A. (2003). Clinical Outcomes Following Laser Photocoagulation Treatment for Diabetic Retinopathy at a Large Australian Ophthalmic Hospital. Clin. Exper. Ophthalmol. 31(4): 305-310.
291. Yu, W., Li, X., She, H., He, P., Dong, J., Rui, M. and Ma, D. (2003). Gene Transfer of Kringle 5 of Plasminogen by Electroporation Inhibits Corneal Neovascularization. Ophthal. Res. 35(5): 239-246.
292. Zelphati, O. and Szoka, F. C. Jr. (1996). Mechanism of Oligonucleotide Release from Cationic Liposomes. Proc. Natl. Acad. Sci. USA 93(21): 11493-11498.
293. Zhang, Y. and Zhang, J. (2005). Surface Modification of Monodisperse Magnetite Nanoparticles for Improved Intracellular Uptake to Breast Cancer Cells. J. Colloid and Interface Sci. 283(2): 352-357.
294. Zhou, X., Klibanov, A. L. and Huang, L. (1991). Lipophilic Polylysines Mediate Efficient DNA Transfection in Mammalian Cells. Biochim. et Biophys. Acta (BBA) - Biomembranes 1065(1): 8-14.
295. Zhu, C., Zhang, Y. and Pardridge, W. M. (2002). Widespread Expression of an Exogenous Gene in the Eye after Intravenous Administration. Investigat. Ophthalmol. Vis. Sci. 43(9): 3075-3080.
296. Zhu, H. L., Stewart, A. S., Taylor, M. D., Vijayasarathy, C., Gardner, T. J. and Sweeney, H. L. (2000). Blocking Free Radical Production Via Adenoviral Gene Transfer Decreases Cardiac Ischemia-Reperfusion Injury. Mol. Ther. 2(5): 470-475.
297. Zweers, M. L. T., Engbers, G. H. M., Grijpma, D. W. and Feijen, J. (2004). In vitro Degradation of Nanoparticles Prepared from Polymers Based on D1-Lactide, Glycolide and Poly(Ethylene Oxide). J. Controlled Rel. 100(3): 347-356.