Gene therapy for ocular neovascularization

Current Gene Therapy

Volumn 7, Issue 1, 2007, Pages 25-33

  Campochiaro, Peter A ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Age related macular degeneration; Angiogenesis; Diabetic retinopathy; Gene therapy; Neovascularization; Proliferative retinopathies

Indexed keywords

ADENOVIRUS VECTOR; ANGIOPOIETIN RECEPTOR; ANGIOSTATIN; DOXYCYCLINE; ENDOSTATIN; LENTIVIRUS VECTOR; PARVOVIRUS VECTOR; PIGMENT EPITHELIUM DERIVED FACTOR; RANIBIZUMAB; SMALL INTERFERING RNA; TAMOXIFEN; TISSUE INHIBITOR OF METALLOPROTEINASE 3; TRANSCRIPTION FACTOR; VASCULOTROPIN RECEPTOR 1; ZINC FINGER PROTEIN;

ANGIOGENESIS; BLINDNESS; CLINICAL TRIAL; DEVELOPED COUNTRY; EYE DISEASE; EYE INFLAMMATION; GENE THERAPY; GENE TRANSFER; GENE VECTOR; HUMAN; INTRAOCULAR PRESSURE; NONHUMAN; PROTEIN EXPRESSION; RETINA MACULA AGE RELATED DEGENERATION; RETINA NEOVASCULARIZATION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SUBRETINAL NEOVASCULARIZATION; TRANSGENE; VIRAL GENE DELIVERY SYSTEM; VISUAL DISORDER;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTIBODIES, MONOCLONAL; CHOROIDAL NEOVASCULARIZATION; DEPENDOVIRUS; DISEASE MODELS, ANIMAL; DRUG ADMINISTRATION ROUTES; ENDOSTATINS; EYE PROTEINS; GENE THERAPY; GENE TRANSFER TECHNIQUES; GENETIC VECTORS; HUMANS; MICE; NERVE GROWTH FACTORS; PROTEASE INHIBITORS; RETINAL NEOVASCULARIZATION; SERPINS; TRANSGENES; VASCULAR ENDOTHELIAL GROWTH FACTORS;

ANIMALIA;

EID: 33847305368     PISSN: 15665232     EISSN: None     Source Type: Journal    
DOI: 10.2174/156652307779940252     Document Type: Review

References (96)

1. Aiello, L. P., Pierce, E. A., Foley, E. D., Takagi, H., Chen, H., Riddle, L., Ferrara, N., King, G. L. and Smith, L. E. H. (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: 10457-10461.
2. Ali, R. R., Reichel, M. B., De Alwis, M., Kanuga, N., Kinnon, C., Levinsky, R. J., Hunt, D. M., Bhattacharya, S. S. and Thrasher, A. J. (1998) Adeno-associated viurs gene transfer to mouse retina. Hum. Gene Ther., 9: 81-86.
3. Alon, T., Hemo, I., Itin, A., Pe'er, J., Stone, J. and Keshet, E. (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat. Med., 1: 1024-1028.
4. Apte, S. S., Olsen, B. R. and Murphy, G. (1995) The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. J. Biol. Chem., 270: 14313-14318.
5. Araki, T., Taniwaki, T., Becerra, S. P., Chader, G. J. and Schwartz, J. P. (1998) Pigment epithelium-derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death. J. Neurosci. Res., 53: 7-15.
6. Auricchio, A., Behling, K. C., Maguire, A. M., O'Conner, E. M., 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: 490-494.
7. Baffert, F., Le, T., Sennino, B., Thruston, G., Kuo, C., Hu-Lowe, D. and McDonald, D.M. (2006) Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am. J. Physiol. Heart Circ. Physiol., 290: 547-559.
8. Baffert, F., Thurston, G., Rochon-Duck, M., Le, T., Brekken, R. and McDonald, D. M. (2004) Age-related changes in vascular endothelial growth factor dependency and angiopoietin-1-induced plasticity of adult blood vessels. Circ. Res., 94: 984-992.
9. Bartosch, B. and Cosset, F.-L. (2004) Strategies for retargeting gene delivery using vectors derived from lentiviruses. Curr. Gene Ther., 4: 427-443.
10. Bennett, J., Duan, D., Engelhardt, J. F. and Maguire, A. M. (1997) Real-time, noninvasive in vivo assessment of adeno-associated virus-mediated retinal transduction. Invest. Ophthalmol. Vis. Sci., 38: 2857-2863.
11. Bilak, M. M., Corse, A. M., Bilak, S. R., Lehar, M., Tombran-Tink, J. and Kuncl, R. W. (1999) Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration. J. Neuropathol. Exp. Neurol., 58: 719-728.
12. Brown, D. M., Kaiser, P. K., Michels, M., Soubrane, G., Heier, J. S., Kim, R. Y., Sy, J. P., Schneider, S. and Group, A. S. (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N. Eng. J. Med., 355: 1432-1444.
13. Bundenz, D. L., Bennett, J., Alonso, L. and Maguire, A. (1995) In vivo gene transfer into murine corneal ednothelial and trabecular meshwork cells. Invest. Ophthalmol. Vis. Sci., 36: 2211-2215.
14. Campochiaro, P. A. (2000) Retinal and choroidal neovascularization. J. Cell Physiol., 184: 301-310.
15. Campochiaro, P. A., Nguyen, Q. D., Shah, S. M., Klein, M. L., Holz, E., Frank, R. N., Saperstein, D. A., Gupta, A., Stout J. T., Macko, J., Di-Bartolomeo, R. and Wei, L. L. (2006) Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial. Hum. Gene Ther., 17: 167-176.
16. Cao, W., Tombran-Tink, J., Elias, R., Sezate, S., Mrazek, D. and McGinnis, J. F. (2001) In vivo protection of photoreceptors from light damage by pigment epithelium-derived factor. Invest. Opthalmol. Vis. Sci., 42: 1642-1652.
17. Cashman, S. M., Bowman, L., Christofferson, J. and Kumar-Singh, R. (2006) Inhibition of choroidal neovascularization by adenovirus-mediated delivery of short hairpin RNAs targeting VEGF as a potential therapy for AMD. Invest. Ophthalmol. Vis. Sci., 47: 3496-3504.
18. Chevez-Barrios, P., Chintagumpala, M., Mieler, W., Paysse, E., Boniuk, M., Kozinetz, C., Hurwith, M. Y. and Hurwitz, R. L. (2005) Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir. J. Clin. Oncol., 23: 7927-7935.
19. Davis, S., Aldrich, T. H., Jones, P., Acheson, A., Ryan, T. E., Bruno, J., Radziejewski, C., Maisonpierre, P. C. and Yancopoulos, G. D. (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell, 87: 1161-1169.
20. Dawson, D. W., Volpert, O. V., Gillis, P., Crawford, S. E., Xu, H.-J., Benedict, W. and Bouck, N. P. (1999) Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science, 285: 245-248.
21. Della, N. G., Campochiaro, P. A. and Zack, D. J. (1996) Localization of TIMP-3 mRNA expression to the retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci., 37: 1921-1924.
22. Fariss, R. N., Apte, S. S., Suthert, P. J., Bird, A. C. and Milam, A. H. (1998) Accumulation of tissue inhibitor of metalloproteinases-3 in human eyes with Sorsby's fundus dystrophy or retinitis pigmentosa. Br. J. Ophthalmol., 82: 1329-1334.
23. Flannery, J. G., Zolotukhin, S., Vaquero, M. I., LaVail, M. M., Muzyczka, N. and Hauswirth, W. W. (1997) Efficient photoreceptor-targeted gene expression in vivo by recominant adeno-associated virus. Proc. Natl. Acad. Sci. USA, 94: 6916-6921.
24. Fukai, N., Eklund, L., Marneros, A. G., Oh, S. P., Keene, D. R., Tamarkin, L., Neiemela, M., Ilves, M., Li, E., Pihlajaniemi, T. and Olsen, B. R. (2002) Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J., 21: 1535-1544.
25. Gao, G., Vandenberghe, L. H. and Wilson, J. M. (2005) New recombinant serotypes of AAV vectors. Curr. Gene Ther., 5: 285-297.
26. Gehlbach, P., Demetriades, A. M., Yamamoto, S., Deering, T., Duh, E. J., Yang, H. S., Cingolani, C., Lai, H., Wei, L. and Campochiaro, P. A. (2003a) Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization. Gene Ther., 10: 637-646.
27. Gehlbach, P., Demetriades, A. M., Yamamoto, S., Deering, T., Xiao, W. H., Duh, E. J., Yang, H. S., Lai, H., Kovesdi, I., Wei, L. and Campochiaro, P. A. (2003b) Periocular gene transfer of sFlt-1 suppresses ocular neovascularization and VEGF-induced breakdown of the blood-retinal barrier. Hum. Gene Ther., 14: 129-141.
28. Green, W. R. and Wilson, D. J. (1986) Choroidal neovascularization. Ophthalmology., 93: 1169-1176.
29. Hangai, M., Moon, Y. S., Kitaya, N., Chan, C. K., Wu, D.-Y., Peters, K. G., Ryan, S. J. and Hinton, D. R. (2001) Systemically expressed soluble Tie2 inhibits intraocular neovascularization. Hum. Gene Ther., 12: 1311-1321.
30. He, Y., Smith, S. K., Day, K. A., Clark, D. E., Licence, D. R. and Charnock-Jones, D. S. (1999) Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre-mRNA is important for the regulation of VEGF activity. Mol. Endocrinol., 13: 537-545.
31. Honda, M., Sakamoto, T., Ishibashi, T., Inomata, H. and Ueno, H. (2000) Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF.flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration. Gene Ther., 7: 978-985.
32. 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 amurine proliferative retinopathy model. Gene Ther., 10: 219-226.
33. Kachi, S., Esumi, N., Zack, D. J. and Campochiaro, P. A. (2006) Sustained expression after nonviral ocular gene transfer using mammalian promoters. Gene Ther., Feb 9 [Epub ahead of print].
34. Kamba, T., Tam, B.Y., Hashizume, H., Haskell, A., Sennino, B., Mancuso, M. R., Norberg, S. M., O'Brien, S. M., Davis, R. B., Gowen, L. C., Anderson, K. D., Thurston, G., Joho, S., Springer, M. L., Kuo, C. J. and McDonald, D. M. (2006) VEGF-dependent plasticity of fenestrated capillaries in the normal adulat microvasculature. Am. J. Physiol. Heart Circ. Physiol., 290: 560-576.
35. Kamei, M. and Hollyfield, J. G. (1999) TIMP-3 in Bruch's membrane: changes during aging and in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci., 40: 2367-2375.
36. Kelly, B. D., Hackett, S. F., Hirota, K., Oshima, Y., Cai, Z., Berg-Dixon, S., Rowan, A., Yan, Z., Campochiaro, P. A. and Semenza, G. L. (2003) Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ. Res., 93: 1074-1081.
37. Kendall, R. L., Wang, G. L. and Thomas, K. A. (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem. Biophys. Res. Comm., 226: 324-328.
38. Kumar-Singh, R. and Chamberlain, J. S. (1996) Encapsidated adenovirus minichromosomes allow delivery and expression of a 14 kb dystrophin cDNA to muscle cells. Hum. Mol. Genet., 5: 913-921.
39. Kwak, N., Okamoto, N., Wood, J. M. and Campochiaro, P. A. (2000) VEGF is an important stimulator in a model of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci., 41: 3158-3164.
40. Lai, C.-C., Wu, W.-C., Chen, S.-L., Xiao, X., Tsai, T.-C., Huan, S.-J., Chen, T.-L., Tsai, R. J.-F. and Tsao, Y.-P. (2001a) Suppression of choroidal neovascularization by adeno-associated virus vector expressing angiostatin. Invest. Ophthalmol. Vis. Sci., 42: 2401-2407.
41. Lai, C.-M., Brankov, M., Zaknich, T., Lai, Y. K.-Y., Shen, W.-Y., Constable, I. J., Kovesdi, I. and Rakoczy, P. E. (2001b) Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization. Hum. Gene. Ther., 12: 1299-1310.
42. Lai, C. M., Shen, W. Y., Brankov, M., Lai, Y. K., Barnett, N. L., Lee, S. Y., Yeo, I. Y., Mathur, R., Ho, J. E., Pineda, P., Barathi, A., Ang, C. L., Constable, I. J. and Rakoczy, E. P. (2005) Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys. Mol. Ther., 12: 659-668.
43. Lai, Y. K., Shen, W. Y., Brankov, M., Lai, C. M., Constable, I. J. and Rakoczy, P. E. (2002) Potential long-term inhibition of ocular neovascularization by recombinant adeno-associated virus-mediated secretion gene therapy. Gene Ther., 9: 804-813.
44. Langton, K. P., Barker, M. D. and McKie, N. (1998) Localization of the functional domains of human tissue inhibitor of metalloptoteinases-3 and the effects of a Sorsby's Fundus Dystrophy mutation. J. Biol. Chem., 273: 16778-16781.
45. Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., Daly, T. J., Davis, S., Sato, T. N. and Yancopoulos, G. D. (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science, 277: 55-60.
46. McLeod, D. S., Taomoto, M., Cao, J., Zhu, Z., Witte, L. and Lutty, G. A. (2002) Localization of VEGF receptor-2 (KDR/Flk-1) and effects of blocking it in oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci., 43: 474-482.
47. Miyoshi, H., Takahashi, M., Gage, F. H. and Verma, I. M. (1997) Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. Proc. Natl. Acad. Sci. USA, 94: 10319-10323.
48. Mori, K., Ando, A., Gehlbach, P., Nesbitt, D., Takahashi, K., Goldsteen, D., Penn, M., Chen, C. T., Melia, M., Phipps, S., Moffat, D., Brazzell, K., Liau, G., Dixon, K. H. and Campochiaro, P. A. (2001a) Inhibition of choroidal neovascularization by intravenous injection of adenoviral vectors expressing secretable endostatin. Am. J. Pathol., 159: 313-20.
49. Mori, K., Duh, E., Gehlbach, P., Ando, A., Takahashi, K., Pearlman, J., Mori, K., Yang, H. S., Zack, D. J., Ettyreddy, D., Brough, D. E., Wei, L. L. and Campochiaro, P. A. (2001b) Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J. Cell. Physiol., 188: 253-263.
50. Mori, K., Gehlbach, P., Ando, A., McVey, D., Wei, L. and A., C. P. (2001c) Regression of ocular neovascularization by increased expression of pigment epithelium-derived factor. Invest. Ophthalmol. Vis. Sci., 43: 2428-2434.
51. Mori, K., Gehlbach, P., Ando, A., Wahlin, K., Gunther, V., McVey, D., Wei, L. and Campochiaro, P. A. (2002a) Intraocular adenoviral vector-mediated gene transfer is increased in proliferative retinopathies. Invest. Ophthalmol. Vis. Sci., 43: 1610-1615.
52. 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. (2002b) AAV-mediated gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization. Invest. Ophthalmol. Vis. Sci., 43: 1994-2000.
53. Naldini, L., Blomer, U., Gage, F. H., Trono, D. and Verma, I. M. (1996) Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc. Natl. Acad. Sci. USA., 93: 11382-11388.
54. Nambu, H., Nambu, R., Oshima, Y., Hackett, S. F., Wiegand, S. J., Yancopoulos, G., Zack, D. J. and Campochiaro, P. A. (2004) Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier. Gene. Ther., 11: 865-873.
55. Nambu, H., Umeda, N., Kachi, S., Oshima, Y., Nambu, R. and Campochiaro, P. A. (2005) Angiopoietin 1 prevents retinal detachment in an aggressive model of proliferative retinopathy, but has no effect on established neovascularization. J. Cell. Physiol., 204: 227-235.
56. Nguyen, Q. D., Shah, S. M., Hafiz, G., Quinlan, E., Sung, J., Chu, K., Cedarbaum, J., Campochiaro, P. A. and Group, C. S. (2006a) A phase 1 trial of intravenously administered VEGF trap for treatment in patients with choroidal neovascularization due to age-related macular degeneration. Ophthalmology, 113: 1522e1-1522e14.
57. Nguyen, Q. D., Tatlipinar, S., Shah, S. M., Haller, J. A., Quinlan, E., Sung, J., Zimmer-Galler, I., Do, D. V. and Campochiaro, P. A. (2006b) Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am. J. Ophthalmol., In press.
58. Oh, H., Takagi, H., Otani, A., Koyama, S., Kemmonchi, S., Uemura, A. and Honda, Y. (2002) Selective induction of neuropilin-1 by vascular endothelial growth factor (VEGF): a mechanism contributing to VEGF-induced angiogenesis. Proc. Natl. Acad. Sci. USA., 99: 383-388.
59. Ohno-Matsui, K., Hirose, A., Yamamoto, S., Saikia, J., Okamoto, N., Gehlbach, P., Duh, E. J., Hackett, S. F., Chang, M., Bok, D., Zack, D. J. and Campochiaro, P. A. (2002) Inducible expression of vascular endothelial growth factor in photoreceptors of adult mice causes severe proliferative retinopathy and retinal detachment. Am. J. Pathol., 160: 711-719.
60. Okamoto, N., Tobe, T., Hackett, S. F., Ozaki, H., Vinores, M. A., LaRochelle, W., Zack, D. J. and Campochiaro, P. A. (1997) Transgenic mice with increased expression of vascular endothelial growth factor in the retina: a new model of intraretinal and subretinal neovascularization. Am. J. Pathol., 151: 281-91.
61. Oosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Dorpe, J. V., Hellings, P., Gorselink, M., Heymans, S., Theilmeier, G., Dewerchin, M., Laudenbach, V., Vermylen, P., Raat, H., Acker, T., Vleminckx, V., Van Den Bosch, L., Cashman, N., Fujisawa, H., Drost, M. R., Sciot, R., Bruyninckx, F., Hicklin, D. J., Ince, C., Gressens, P., Lupu, F., Plate, K. H., Robberecht, W., Herbert, J.-M., Collen, D. and Carmeliet, P. (2001) Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat. Genet., 28: 131-138.
62. O'Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., Flynn, E., Birknead, J. R., Olsen, B. R. and Folkman, J. (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell, 88: 277-285.
63. O'Reilly, M. S., Holmgren, S., Shing, Y., Chen, C., Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, H. E. and Folkman, J. (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell, 79: 315-328.
64. Oshima, Y., Deering, T., Oshima, S., Nambu, H., Reddy, P. S., Kaleko, M., Connelly, S., Hackett, S. F. and Campochiaro, P. A. (2004a) Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor. J. Cell Physiol., 199: 412-417.
65. Oshima, Y., Oshima, S., Nambu, H., Kachi, S., Hackett, S. F., Melia, M., Kaleko, M., Connelly, S., Esumi, N., Zack, D. J. and Campochiaro, P. A. (2004b) Increased expression of VEGF in retinal pigmented epithelial cells is not sufficient to cause choroidal neovascularization. J. Cell Physiol., 201: 393-400.
66. Oshima, Y., Oshima, S., Nambu, H., Kachi, S., Takahashi, K., Umeda, N., Shen, J., Dong, A., Apte, R. S., Duh, E., Hackett, S. F., Okoye, G., Ishibashi, K., Handa, J., Melia, M., Wiegand, S., Yancopoulos, G., Zack, D. J. and Campochiaro, P. A. (2005) Different effects of angiopoietin 2 in different vascular beds in the eye new vessels are most sensitive. FASEB J., 19: 963-965.
67. Ozaki, H., Seo, M.-S., Ozaki, K., Yamada, H., Yamada, E., Hofmann, F., Wood, J. and Campochiaro, P. A. (2000) Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization. Am. J. Pathol., 156: 679-707.
68. Ozaki, H., Yu, A., Della, N., Ozaki, K., Luna, J. D., Yamada, H., Hackett, S. F., Okamoto, N., Zack, D. J., Semenza, G. L. and Campochiaro, P. A. (1999) Hypoxia inducible factor-1a is increased in ischemic retina: temporal and spatial correlation with VEGF expression. Invest. Ophthalmol. Vis. Sci., 40: 182-189.
69. Pozansky, M., Lever, A., Bergeron, L., Hazeltine, W. and Sodroski, J. (1991) Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector. J. Virol., 65: 532-536.
70. 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. Natil. Acad. Sci. USA, 99: 8909-8914.
71. Reich, S. J., Fosnot, J., Kuroki, A., Tang, W., Yang, X., Maguire, A. M., Bennett, J. and Tolentino, M. J. (2003) Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol. Vis., 9: 210-216.
72. Rosenfeld, P. J., Brown, D. M., Heier, J. S., Boyer, D. S., Kaiser, P. K., Chung, C. Y., Kim, R. Y. and Group, M. S. (2006) Ranibizumab for neovascular age-related macular degeneration. N. Eng. J. Med., 355: 1419-1431.
73. Rota, R., Riccioni, T., Zaccarini, M., Lamartina, S., Gallo, A. D., Fusco, A., Kovesdi, I., Balestrazzi, E., Abeni, D. C., Ali, R. R. and Capogrossi, M. C. (2004) Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer. J. Gene Med., 6: 992-1002.
74. Saishin, Y., Lima Silva, R., Saishin, Y., Callahan, K., Schoch, C., Ahlheim, M., Lai, H., Kane, F., Brazzell, R., K., Bodmer, D. and Campochiaro, P. A. (2003a) Periocular injection of microspheres containing PKC412 inhibits choroidal neovascularization in a porcine model. Invest. Ophthalmol. Vis. Sci., 44: 4989-4993.
75. R1R2 suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier. J. Cell Physiol., 195: 241-248.
76. Seo, M.-S., Kwak, N., Ozaki, H., Yamada, H., Okamoto, N., Fabbro, D., Hofmann, F., Wood, J. M. and Campochiaro, P. A. (1999) Dramatic inhibition of retinal and choroidal neovascularization by oral administration of a kinase inhibitor. Am. J. Pathol., 154: 1743-1753.
77. Shen, J., Samul, R., Lima e Silva, R., Akiyama, H., Liu, H., Saishin, Y., Hackett, S. F., Zinnen, S., Kossen, K., Fosnaugh, K., Vargeese, C., Aitchison, R., Pavco, P. and Campochiaro, P. A. (2005) Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Ther., 13: 225-234.
78. Shen, J., Samul, R., Zimmer, J., Liu, H., Liang, X., Hackett, S. F. and A., C. P. (2004) Deficiency of neuropilin 2 suppresses VEGF-induced retinal neovascularization. Mol. Med., 10: 12-18.
79. Shen, J., Yang, X. R., Xiao, W. H., Hackett, S. F., Sato, Y. and Campochiaro, P. A. (2006) Vasohibin is up-regulated by VEGF in the retina and suppresses VEGF receptor 2 and retinal neovascularization. FASEB J., 20: 723-725.
80. Shimizu, K., Kobayashi, Y. and Muraoka, K. (1981) Midperipheral fundus involvement in diabetic retinopathy. Ophthalmology, 88: 601-612.
81. Smith, L. E. H., Wesolowski, E., McLellan, A., Kostyk, S. K., D'Amato, R., Sullivan, R. and D'Amore, P. A. (1994) Oxygen-induced retinopathy in the mouse. Invest. Ophthalmol. Vis. Sci., 35: 101-111.
82. Soboleva, G., Geis, B., Schrewe, H. and Weber, B. H. F. (2003) Sorsby fundus dystrophy mutation Timp3s156C affects the morphological and biochemical phenotype but not metalloproteinase homeostasis. J. Cell Physiol., 197: 149-156.
83. Steele, F. R., Chader, G. J., Johnson, L. V. and Tombran-Tink, J. (1993) Pigment epithelium-derived factor: neurotrophic activity and identification as a member or the serine protease inhibitor gene family. Proc. Natl. Acad. Sci. USA, 90: 1526-1530.
84. Takahashi, K., Luo, T., Saishin, Y., Y., S., Sung, J., Hackett, S. F., Brazzell, R. K., Kaleko, M. and Campochiaro, P. A. (2002) Sustained transduction of ocular cells with a bovine immunodeficiency viral vector. Hum. Gene Ther., 13: 1305-1316.
85. Takahashi, K., Saishin, Y., Saishin, Y., Lima Silva, R., Oshima, Y., Oshima, S., Melia, M., Paszkiet, B., Zerby, D., Kadan, M. J., Liau, G., Kaleko, M., Connelly, S., Luo, T. and Campochiaro, P. A. (2003) Intraocular expression of endostatin reduces VEGF-induced retinal vascular permeability, neovascularization, and retinal detachment. FASEB J., 17: 896-898.
86. Takahashi, T., Nakamura, T., Hayashi, A., Kamei, M., Nakabayashi, M., Okada, A. A., Tomita, N., Daneda, Y. and Tano, Y. (2000) Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium. Am. J. Ophthalmol., 130: 774-781.
87. Tan, S., Guschin, D., Davalos, A., Lee, Y.-L., W., S. A., Jouvenot, Y., Zhang, H. S., Isalan, M., Berg, L.-P., Campos, B., Hong, Q., Spratt, S. K., Case, C. C., Pabo, C. O., Campisi, J. and Gregory, P. D. (2003) Zinc-finger protein-targeted gene regulation: genomewide single-gene specificity. Proc. Natl. Acad. Sci. USA, 100: 11997-12002.
88. Tobe, T., Ortega, S., Luna, J. D., Ozaki, H., Okamoto, N., Derevjanik, N. L., Vinores, S. A., Basilico, C. and Campochiaro, P. A. (1998) Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model. Am. J. Pathol., 153: 1641-1646.
89. Tomanin, R. and Scarpa, M. (2004) Why do we need new gene therapy viral vectors? Characteristics, limitations and future perspectives of viral vector transduction. Curr. Gene Ther., 4: 357-372.
90. Tombran-Tink, J., Chader, G. G. and Johnson, S. V. (1991) PEDF: a pigment epithelium derived factor with potent neuronal differentiating activity. Exp. Eye. Res., 53: 411-414.
91. Watanabe, K., Hasegawa, Y., Yamashita, H., Shimizu, K., Ding, Y., Abe, M., Ohta, H., Imagawa, K., Hojo, K., Maki, H., Sonoda, H. and Sato, Y. (2004) Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J. Clin. Invest., 114: 898-907.
92. Weber, B. H. F., Vogt, G., Pruett, R. C., Stohr, H. and Felbor, U. (1994) Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat. Genet., 8: 352-356.
93. Yamada, H., Yamada, E., Kwak, N., Ando, A., Suzuki, A., Esumi, N., Zack, D. J. and Campochiaro, P. A. (2000) Cell injury unmasks a latent proangiogenic phenotype in mice with increased expression of FGF2 in the retina. J. Cell Physiol., 185: 135-142.
94. Yang, G. S., Schmidt, M., Yan, Z., Lindbloom, J. D., Harding, T. C., Donahue, B. A., Engelhardt, J. F., Kotin, R. and Davidson, B. A. (2002) Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size. J. Virol., 76: 7651-7660.
95. Yannuzzi, L. A., Negrao, S., Iida, T., Carvalho, C., Rodriguez-Coleman, H., Slakter, J. S., Freund, K. B., Sorenson, J., Orlock, D. and Borodoker, N. (2001) Retinal angiomatous proliferation in age-related macular degeneration. Retina., 21: 416-434.
96. Zhang, H. S., Kachi, S., Kachi, M., Liu, P.-Q., Akiyama, H., Umeda, N., Yokoi, K., Hackett, S. F., Gregory, P. D. and Campochiaro, P. A. (2006) Engineered zinc finger protein transption factors as a potential therapy for ocular neovascularization. ARVO abstract 1786.