Phenotypes and biomarkers of diabetic retinopathy

Progress in Retinal and Eye Research

Volumn 41, Issue , 2014, Pages 90-111

  Cunha Vaz, José ^a,b   Ribeiro, Luisa ^a,b   Lobo, Conceição ^a,b  

^a ASSOCIATION FOR INNOVATION AND BIOMEDICAL RESEARCH ON LIGHT AND IMAGE AIBILI   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

Biomarkers; Diabetic retinopathy; Macular edema; Microaneurysm; Optical coherence tomography; Phenotypes

Indexed keywords

BIOLOGICAL MARKER; HEMOGLOBIN A1C;

ANGIOGENESIS; APOPTOSIS; BLOOD RETINA BARRIER; DIABETIC MACULAR EDEMA; DIABETIC RETINOPATHY; HUMAN; HYPOXIA; INFLAMMATION; MACULAR EDEMA; MICROANEURYSM; NEUROPATHY; NONPROLIFERATIVE DIABETIC RETINOPATHY; OPTICAL COHERENCE TOMOGRAPHY; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; RETINA INJURY; REVIEW; VISUAL IMPAIRMENT; ANEURYSM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; VISUAL ACUITY;

ANEURYSM; BIOLOGICAL MARKERS; DIABETIC RETINOPATHY; HUMANS; MACULAR EDEMA; PHENOTYPE; TOMOGRAPHY, OPTICAL COHERENCE; VISUAL ACUITY;

EID: 84925546470     PISSN: 13509462     EISSN: 18731635     Source Type: Journal    
DOI: 10.1016/j.preteyeres.2014.03.003     Document Type: Review

References (226)

1. Adamis A.P. Is diabetic retinopathy an inflammatory disease?. Br. J. Ophthalmol. 2002, 86(4):363-365.
2. Aiello L.P., Gardner T.W., King G.L., Blankenship G., Cavallerano J.D., Ferris F.L., Klein R. Diabetic retinopathy. Diabetes Care 1998, 21:143-156.
3. Alkuraya H., Kangave D., Abu El-Asrar A.M. The correlation between coherence tomography features and severity of retinopathy, macular thickness and visual acuity in diabetic macular edema. Int. Ophthalmol. 2005, 26(3):93-99.
4. ® guidelines. Diabetic retinopathy 2008, American Academy of Ophthalmology Retina Panel, (4th printing 2012), American Academy of Ophthalmology, San Franscisco, CA, Available at:. http://one.aao.org/preferred-practice-pattern/diabetic-retinopathy-ppp-september-2008-4th-print.
5. Antonetti D.A., Barber A.J., Bronson S.K., Freeman W.M., Gardner T.W., Jefferson L.S., Kester M., Kimball S.R., Krady J.K., LaNoue K.F., Norbury C.C., Quinn P.G., Sandirasegarane L., Simpson I.A. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 2006, 55:2401-2411.
6. Antonetti D.A., Klein R., Gardner T.W. Diabetic retinopathy. N. Engl. J. Med. 2012, 366:1227-1239.
7. Arden G.B., Hamilton A.M., Wilson-Holt J., Ryan S., Yudkin J.S., Kurtz A. Pattern electroretinograms become abnormal when background diabetic retinopathy deteriorates to a preproliferative stage: possible use as a screening test. Br. J. Ophthalmol. 1986, 70:330-335.
8. Ashton N. Arteriolar involvement in diabetic retinopathy. Br. J. Ophthalmol. 1953, 37:282-292.
9. Ashton N. Diabetic microangiopathy. Adv. Ophthalmol. 1958, 8:1-84.
10. Ashton N. Vascular basement membrane changes in diabetic retinopathy. Montgomery Lecture, 1973. Br. J. Ophthalmol. 1974, 58:344-347.
11. Arar N.H., Freedman B.I., Adler S.G., Iyengar S.K., Chew E.Y., Davis M.D., Satko S.G., Bowden D.W., Duggirala R., Elston R.C., Guo X., Hanson R.L., Igo R.P., Ipp E., Kimmel P.L., Knowler W.C., Molineros J., Nelson R.G., Pahl M.V., Quade S.R., Rasooly R.S., Rotter J.I., Saad M.F., Scavini M., Schelling J.R., Sedor J.R., Shah V.O., Zager P.G., Abboud H.E. Heritability of the severity of diabetic retinopathy: the FIND-Eye study. Invest. Ophthalmol. Vis. Sci. 2008, 49:3839-3845. Family Investigation of Nephropathy and Diabetes Research Group.
12. Aydin E., Demir H.D., Ozyurt H., Etikan I. Association of plasma homocysteine and macular edema in type 2 diabetes mellitus. Eur. J. Ophthalmol. 2008, 18(2):226-232.
13. Baek K.J., Thiel B.A., Lucas S., Stuehr D.J. Macrophage nitric oxide synthase subunits. Purification, characterization, and role of prosthetic groups and substrate in regulating their association into a dimeric enzyme. J. Biol. Chem. 1993, 268:21120-21129.
14. Bai Y., Ma J.X., Guo J., Wang J., Zhu M., Chen Y., Le Y.Z. Muller cell-derived VEGF is a significant contributor to retinal neovascularization. J. Pathol. 2009, 219:446-454.
15. Barber A.J., Lieth E., Khin S.A., Antonetti D.A., Buchanan A.G., Gardner T.W. Neural apoptosis in the retina during experimental and human diabetes: early onset and effect of insulin. J. Clin. Invest 1998, 102:783-791.
16. Barber A.J. Anew view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog. Neuropsychopharmacol. Biol. Psychiatry 2003, 27(2):283-290.
17. Barber A.J., Gardner T.W., Abcouwer S.F. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2011, 52(2):1156-1163.
18. Bearse M.A., Han Y., Schneck M.E., Adams A.J. Retinal function in Normal and diabetic eyes mapped with the slow flash multifocal electroretinogram. Invest. Ophthalmol. Vis. Sci. 2004, 45(1):296-304.
19. Bearse M.A., Adams A.J., Han Y., Schneck M.E., Ng J., Bronson-Castain K., Barez S. Amultifocal electroretinogram model predicting the development of diabetic retinopathy. Prog. Retin. Eye Res. 2006, 25:425-448.
20. Benson W.E., Brown G.C., Tasman W. Diabetes and its Ocular Complications 1988, WR Saubders Company, Philadelphia.
21. Bernardes R., Lobo C., Cunha-Vaz J.G. Multimodal macula mapping. A new approach to study diseases of the macula. Surv. Ophthalmol. 2002, 47:580-589.
22. Bernardes R., Nunes S., Pereira I., Torrent T., Rosa A., Coelho D., Cunha-Vaz J. Computer-assisted microaneurysm turnover in the early stages of diabetic retinopathy. Ophthalmologica 2009, 223:284-291.
23. Bernardes R., Santos T., Serranho P., Lobo C., Cunha-Vaz J. Noninvasive evaluation of retinal leakage using OCT. Ophthalmologica 2011, 226:29-36.
24. Blom J.J., Giove T.J., Favazza T.L., Akula J.D., Eldred W.D. Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy. J. Ocul. Biol. Dis. Infor. 2011, 4(1-2):70-82.
25. Boehm B.O., Schilling S., Rosinger S., Lang G.E., Lang G.K., Kientsch-Engel R., Stahl P. Elevated serum levels of N(epsilon)-carboxymethyl-lysine, n advanced glycation end product, are associated with proliferative diabetic retinopathy and macular oedema. Diabetologia 2004, 47(8):1376-1379.
26. Boeri D., Maiello M., Lorenzi M. Increased prevalence of microthromboses in retinal capillaries of diabetic individuals. Diabetes 2001, 50:1432-1439.
27. Bolz M., Ritter M., Schneider M., Simader C., Scholda C., Schmidt-Erfurth U. Asystematic correlation of angiography and high-resolution optical coherence tomography in diabetic macular edema. Ophthalmology 2009, 116(1):66-72.
28. Brazionis L., Rowlet K., Itsiopoulos C., Harper C.A., O'Dea K. Homocysteine and diabetic retinopathy. Diabetes Care 2008, 31(1):50-56.
29. Bressler N.M., Miller K.M., Beck R.W., Bressler S.B., Glassman A.R., Kitchens J.W., Melia M., Schlossman D.K. Diabetic retinopathy clinical research network: observational study of subclinical diabetic macular edema. Eye 2012, 26(6):833-840.
30. Bronson-Castain K.W., Bearse M.A., Neuville J., Jonasdottir S., King-Hooper B., Barez S., Schneck M.E., Adams A.J. Adolescents with Type 2 diabetes: early indications of focal retinal neuropathy, retinal thinning, and venular dilation. Retina 2009, 29:618-626.
31. Brown D.M., Nguyen Q.D., Marcus D.M., Boyer D.S., Patel S., Feiner L., Schlottmann P.G., Rundle A.C., Zhang J., Rubio R.G., Adamis A.P., Ehrlich J.S., Hopkins J.J. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 2013, 120(10):2013-2022. RIDE and RISE Research Group.
32. Browning D.J., Fraser C.M. The predictive value of patient and eye characteristics on the course of subclinical macular edema. Am. J. Ophthalmol. 2008, 145:149-154.
33. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414:813-820.
34. Burris C., Klug K., Ngo I.T., Sterling P., Schein S. How Müller glial cells in macaque fovea coat and isolate the synaptic terminals of cone photoreceptors. J. Comp. Neurol. 2002, 453(1):100-111.
35. Butt A., Ahmad M.S., Powrie J., Swaminathan R. Assessment of diabetic retinopathy by measuring retina-specific mRNA in blood. Expert Opin. Biol. Ther. Suppl.1 2012, S79-S84.
36. Campochiaro P.A., Brown D.M., Pearson A., Ciulla T., Boyer D., Holz F.G., Tolentino M., Gupta A., Duarte L., Madreperla S., Gonder J., Kapik B., Billman K., Kane F.E. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmol 2011, 118(4). FAME Study Group, 626-635.e2.
37. Carmo A., Ramos P., Reis A., Proença R., Cunha-vaz J.G. Breakdown of the inner and outer blood retinal barrier in streptozotocin-induced diabetes. Exp. Eye Res. 1998, 67:569-575.
38. Cervia D., Catalani E., Dal Monte M., Casini G. Vascular endothelial growth factor in the ischemic retina and its regulation by somatostatin. J. Neurochem. 2012, 120(5):818-829.
39. Chen L., Zhang S.S., Barnstable C.J., Tombran-Tink J. PEDF induces apoptosis in human endothelial cells by activating p38 MAP kinase dependent cleavage of multiple caspases. Biochem. Biophys. Res. Commun. 2006, 348(4):1288-1295.
40. Chowdhury T.A., Hopkins D., Dodson P.M., Vafidis G.C. The role of serum lipids in exudative diabetic maculapathy: is there a place for lipid lowering therapy?. Eye 2002, 16:693-698.
41. Cikamatana L., Mitchell P., Rochtchina E., Foran S., Wang J.J. Five-year incidence and progression of diabetic retinopathy in a defined older population: the Blue Mountains Eye Study. Eye 2007, 21:465-471.
42. Clermont A., Chilcote T.J., Kita T., Liu J., Riva P., Sinha S., Feener E.P. Plasma kallikrein mediates retinal vasculature disfunction and induces retinal thickening in diabetic rats. Diabetes 2011, 60:1590-1598.
43. Costagliola C., Romano V., DeTollis M., Aceto F., dell'Omo R., Romano M.R., Pedicino C., Semerano F. TNF-alpha levels in tears: a novel biomarker to asses the degree of diabetic retinopathy. Mediat. Inflamm. 2013, 2013:629529.
44. Cui J.Z., Chiu A., Maberley D., Ma P., Samad A., Matsubara J.A. Stage specificity of novel growth factor expressionduring development of proliferative viitreoretinopathy. Eye 2007, 21:200-208.
45. Cunha-Vaz J.G., Maurice D.M. Fluorescein transport by retinal vessels. J. Physiol. 1965, 183:42-43.
46. Cunha-Vaz J.G., Maurice D.M. Fluorescein transport by retinal vessels. Proc 20 Internat Congr Ophthalmol (Excerpta Medica International Congress Series) 1967, vol. 146:187-188.
47. Cunha-Vaz J.G., Faria de Abreu J.R., Campos A.J., Figo G.M. Early breakdown of the blood-retinal barrier in diabetes. Br. J. Ophthalmol. 1975, 59:649-656.
48. Cunha-Vaz J.G. Pathophysiology of diabetic retinopathy. Br. J. Ophthalmol. 1978, 62:351-355.
49. Cunha-Vaz J.G. The blood-ocular barriers. Serv. Ophthalmol. 1979, 23:279-296.
50. Cunha-Vaz J.G., Goldberg M.F., Vygantas C., Noth J. Early detection of retinal involvement in diabetes by vitreous fluorophotometry. Ophthalmology 1979, 86:264-275.
51. Cunha-Vaz J.G., Travassos A. Breakdown of the blood-retinal barriers and cystoid macular edema. Surv. Ophthalmol. 1984, 28:485-492.
52. Cunha-Vaz J.G. Diabetic retinopathy. Microvascular and Neurological Complications of Diabetes. Press/Springer Verlag, Padova, Liviana 1986, 3. G. Crepaldi, J.G. Cunha-Vaz, D. Fedele, C. Morgensen, S. Ward (Eds.).
53. Cunha-Vaz J.G. Blood-retinal barrier in diabetes. Diabetic Retinopathy. Taylor & Francis, A Martin Dunitz, London 2000, 155-168. P. van Bijsterveld (Ed.).
54. Cunha-Vaz J.G. Diabetic retinopathy: surrogate outcomes for drug development for diabetic retinopathy. Ophthalmologica 2000, 214:377-380.
55. Cunha-Vaz J.G., Bernardes R. Nonproliferative retinopathy in diabetes type 2. Initial stages and characterization of phenotypes. Progr. Retin. Eye Res. 2005, 24:355-377.
56. Cunha-Vaz J.G. Characterization and relevance of different diabetic retinopathy phenotypes. Dev. Ophthalmol. 2007, 39:13-30.
57. Curcio C.A., Allen K.A. Topography of ganglion cells in human retina. J. Comp. Neurol. 1990, 300:5-21.
58. Curcio C.A., Sloan K.R., Kalina R.E., Hendrickson A.E. Human receptor topography. J. Comp. Neurol. 1990, 292:497-523.
59. Curtis T.M., Gardiner T.A., Stitt A.W. Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?. Eye 2009, 23:1496-1508.
60. Daley M.L., Watzke R.C., Riddle M.C. Early loss of blue-sensitive color vision in patients with type I diabetes. Diabetes Care 1987, 10:777-781.
61. Ditzel J. Oxygen transport impairment in diabetes. Diabetes 1976, 25(2 Suppl.):832-838.
62. Dorner G.T., Garhofer G., Kiss B., Polska E., Polak K., Riva C.E., Schmetterer L. Nitric oxide regulates retinal vascular tone in humans. Am. J. Physiol. Heart Circ. Physiol. 2003, 285:H631-H636.
63. DRCRnet - The Diabetic Retinopathy Clinical Research Network Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Opthalmology 2010, 117(6). 1064-1077.e35.
64. Du X.L., Edelstein D., Rossetti L., Fantus I.G., Goldberg H., Ziyadeh F., Wu J., Brownlee M. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:12222-12226.
65. Ejaz S., Chekarova I., Ejaz A., Sohail A., Lim C.W. Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy. Diabetes Obes. Metab. 2008, 10:53-63.
66. Engerman R., Bloodworth J.M., Nelson S. Relationship of microvascular disease in diabetes to metabolic control. Diabetes 1977, 26:760-769.
67. Engerman R.L., Kern T.S. Experimental galactosemia produces diabetic-like retinopathy. Diabetes 1984, 33:97-100.
68. Engerman R.L., Kern T.S. Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosemic dogs. Diabetes 1993, 42:820-825.
69. Everitt B. Commentary: classification and cluster analysis. Br. Med. J. 1995, 311:535-536.
70. Feldt-Rasmussen B. Microalbuminuria. Int. Diabetes Monit. 2007, 19(2):1-2.
71. Feng Y., Wang Y., Stock O., Pfister F., Tanimoto N., Seeliger M.W., Hillebrands J.L., Hoffmann S., Wolburg H., Gretz N., Hammes H.P. Vasoregression linked to neuronal damage in the rat with defect of polycystin-2. PLoS One 2009, 4(10):e7328.
72. Fong D.S., Aiello L., Gardner T.W., King G.L., Blankenship G., Cavallerano J.D., Ferris F.L., Klein R., for the American Diabetes Association Retinopathy in diabetes. Diabetes Care 2004, 27(Suppl.1):S84-S87.
73. Fong D.S., Aiello L.P., Ferris F.L., Klein R. Diabetic retinopathy. Diabetes Care 2004, 27:2540-2553.
74. Frisen F.M. Asimple relationship between the probability distribution of visual acuity and the density of retinal output channels. Acta Ophthalmol. 1976, 54:437-444.
75. Gardiner T.A., Archer D.B., Curtis T.M., Stitt A.W. Arteriolar involvement in the microvascular lesions of diabetic retinopathy: implications for pathogenesis. Microcirculation 2007, 14(1):25-38.
76. Gerhardinger C., Costa M.B., Coulombe M.C., Toth I., Hoehn T., Grosu P. Expression of acute-phase response proteins in retinal Müller cells in diabetes. Invest. Ophthalmol. Vis. Sci. 2005, 46(1):349-357.
77. Ghanem A.A., Elewa A., Arafa L.F. Pentosidine and N-carboxymethyl-lysine: biomarkers for type 2 diabetic retinopathy. Eur. J. Ophthalmol. 2011, 21(1):48-54.
78. Ghattas A., Lip P.L., Lip G.Y. Renin-angiotensin blockade in diabetic retinopathy. Int. J. Clin. Pract. 2011, 65(2):113-116.
79. Ghazi N.G., Ciralsky J.B., Shah S.M., Campochiaro P.A., Haller J.A. Optical coherence tomography findings in persistant diabetic macular edema: the vitreomacular interface. Am. J. Ophthalmol. 2007, 144:747-754.
80. Goldstein M., Leibovitch I., Yeffimov I., Gavendo S., Sela B.A., Loewenstein A. Hyperhomocysteinemia in patients with diabetes mellitus with and without diabetic retinopathy. Eye (Lond) 2004, 18(5):460-465.
81. Gowda K., Zinnanti W.J., LaNoue K.J. The influence of diabetes on glutamate metabolism in retinas. J. Neurochem. 2011, 117:309-320.
82. Grange J.D. Retinopathie Diabétique: Rapport à la Societé Française d'Ophthalmologie 1995, Masson, Paris.
83. Hamaoui K., Butt A., Powrie J., Swaminathan R. Concentration of ciruclating rhodopsin mRNA in diabetic retinopathy. Clin. Chem. 2004, 50:2152-2155.
84. Hammes H.P. Pericytes and the pathogenesis of diabetic retinopathy. Horm. Metab. Res. Suppl. 2005, 1:39-43.
85. Hammes H.P., Feng Y., Pfister F., Brownlee M. Diabetic retinopathy: targeting vasoregression. Diabetes 2011, 60:9-16.
86. Han Y., Bearse M.A., Schneck M.E., Barez S., Jacobsen C.H., Adams A.J. Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2004, 45:948-954.
87. Han Y., Schneck M.E., Bearse M.A., Barez S., Jacobsen C.H., Jewell N.P., Adams A.J. Formulation and evaluation of a predictive model to identify the sites of future diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2004, 45:4106-4112.
88. Harhaj N.S., Felinski E.A., Wolpert E.B., Sundstrom J.M., Gardner T.W., Antonetti D.A. VEGF activation of protein kinase C stimulates occluding phosphorylation and contributes to endothelial permeability. Invest. Ophthalmol. Vis. Sci. 2006, 47:5106-5115.
89. Haritoglou C., Kernt M., Neubauer A., Gerss J., Oliveira C.M., Kampik A., Ulbig M. Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy. Retina 2014, 34(1):157-164.
90. Harrison W.W., Bearse M.A., Ng J.S., Jewell N.P., Barez S., Burger D., Schneck M.E., Adams A.J. Multifocal electroretinograms predict onset of diabetic retinopathy in adult patients with diabetes. Invest. Ophthalmol. Vis. Sci. 2011, 52:772-777.
91. Harrison W.W., Bearse M.A., Schneck M.E., Wolf B.E., Jewel N.P., Barez S., Mick A.B., Dolan B.J., Adams A.J. Prediction, by retinal location, of the onset of diabetic edema in patients with nonproliferative diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2011, 52(9):6825-6831.
92. Heath H., Brigden W.D., Canever J.V., Pollock J., Junter P.R., Helsey J., Bloom A. Platelet adhesiveness and aggregation in relation to diabetic retinopathy. Diabetologia 1971, 7:308-315.
93. Hee M.R., Puliafito C.A., Wong C., Duker J.S., Reichel E., Rutledge B., Schuman J.S., Swanson E.A., Fujimoto J.G. Quantitative assessment of macular edema with optical coherence tomography. Arch. Ophthalmol. 1995, 113:1019-1029.
94. Heintz E., Wiréhn A.B., Peebo B.B., Rosenqvist U., Levin L.A. Prevalence and healthcare costs of diabetic retinopathy: a population-based register study in Sweden. Diabetologia 2010, 53:2147-2154.
95. Hellstedt T., Immonen I. Disappearance and formation rates of microaneurysms in early diabetic retinopathy. Br. J. Ophthalmol. 1996, 80:135-139.
96. Hellström A., Svensson E., Carlsson B., Niklasson A., Albertsson-Wikland K. Reduced retinal vascularization in children with growth hormone deficiency. J. Clin. Endocrinol. Metab. 1999, 84(2):795-798.
97. Helmholtz H. Helmholtz's Treatise on Physiological Optics. The Sensations of Vision. Trans. J. P. C. Southall 1924, vol. II. Optical Society of America, New York.
98. Hietala K., Forsblom C., Summanen P., Groop P.H. Heritability of proliferative diabetic retinopathy. Diabetes 2008, 57:2176-2180. on behalf of the FinnDiane Study Group.
99. Hirsch I., Bownlee M. Beyond haemoglobin A1c - need for additional markers of risk for diabetic microvascular complications. JAMA 2010, 303(22):2291-2292.
100. Hood D.C., Frishman L.J., Saszik S., Viswanathan S. Retinal origins of the primate multifocal ERG: implications for the human response. Invest. Ophthalmol. Vis. Sci. 2002, 43:1673-1685.
101. Hove M.N., Kristensen J.K., Lauritzen T., Bek T. The relationships between risk factors and the distribution of retinopathy lesions in type 2 diabetes. Acta Ophthalmol. Scand. 2006, 84(5):619-623.
102. Ibrahim A.S., El-Remessy A.B., Matragoon S., Zhang W., Patel Y., Khan S., Al-Gayyar M.M., El-Shishtawy M.M., Liou G.I. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes. Diabetes 2011, 60(4):1122-1133.
103. Imai H., Singh R.S., Fort P.E., Gardner T.W. Neuroprotection for diabetic retinopathy. Dev. Ophthalmol. 2009, 44:56-68.
104. International Diabetes Federation IDF Diabetes Atlas 2013, vol. 2013. International Diabetes Federation, Brussels, Belgium. http://www.idf.org/diabetesatlas, sixth ed.
105. Ishibashi T., Tanaka K., Tanoguchi Y. Platelet aggregation and coagulation in the pathogenesis of diabetic retinopathy in rats. Diabetes 1981, 30:601-606.
106. Ishii H., Jirousek M.R., Koya D., Takagi C., Xia P., Clermont A., Bursell S.E., Kern T.S., Ballas L.M., Heath W.F., Stramm L.E., Feener E.P., King G.L. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 1996, 272(5262):728-731.
107. Javitt J.C.C., Aiello L.P. Cost-effectiveness of detecting and treating diabetic retinopathy. Am. Int. Med. 1996, 124:164-169.
108. Joussen A.M., Poulaki V., Qin W., Kirchhof B., Mitsiades N., Wiegand S.J., Rudge J., Yancopoulos G.D., Adamis A.P. Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion invivo. Am. J. Pathol. 2002, 160(2):501-509.
109. Joussen A.M., Poulaki V., Le M.L., Koizumi K., Esser C., Janicki H., Schraermeyer U., Kociok N., Fauser S., Kirchhof B., Kern T.S., Adamis A.P. Acentral role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004, 18(12):1450-1452.
110. Kador P.F., Akagi Y., Takahashi Y., Ikebe H., Wyman M., Kinoshita J.H. Prevention of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by aldose reductase inhibitors. Arch. Ophthalmol. 1990, 108:1301-1309.
111. Kaufman L., Rouseeuw P. Finding Groups in Data: an Introduction to Cluster Analysis 1990, John Wiley & Sons Inc., New York.
112. Kaur C., Foulds W.S., Ling E.A. Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management. Prog. Retin. Eye Res. 2008, 27(6):622-647.
113. Kempen J.H., O'Colmain B.J., Leske M.C., Haffner S.M., Klein R., Moss S.E., Taylor H.R., Hamman R.F. The prevalence of diabetic retinopathy among adults in the United States. Arch. Ophthalmol. 2004, 122:552-563. Eye Diseases Prevalence Research Group.
114. Kern T.S., Engerman R.L. Amouse model of diabetic retinopathy. Arch. Ophthalmol. 1996, 114:986-990.
115. Kern T.S. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp. Diabetes Res. 2007, 2007:95103.
116. Klaassen I., Van Noorden C.J., Schlingemann R.O. Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog. Retin. Eye Res. 2013, 34:19-48.
117. Klein R., Meuer S.M., Scot E., Moss M.A., Klein B.E.K. The relationship of retinal microaneurysm counts to the 4-year progression of diabetic retinopathy. Arch. Ophthalmol. 1989, 107:1780-1785.
118. Klein R., Klein B.E.K., Moss S.E., Cruikschanks K.J. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 1995, 102:7-16.
119. Klein R., Meuer S.M., Moss S.E., Klein B.E.K. Retinal microaneurysms counts and 10-year progression of diabetic retinopathy. Arch. Ophthalmol. 1995, 113:1386-1391.
120. Klein B.E., Knudtson M.D., Tsai M.Y., Klein R. The relation of markers of inflammation and endothelial dysfunction to the prevalence and progression of diabetic retinopathy: Wisconsin epidemiologic study of diabetic retinopathy. Arch. Ophthalmol. 2009, 127(9):1175-1182.
121. Kohner E.M., Henkind P. Correlation of fluorescein angiogram and retinal digest in diabetic retinopathy. Am. J. Ophthalmol. 1970, 69:403-414.
122. Kohner E.M., Sleightholm M. Does microaneurysm count reflect severity of early diabetic retinopathy?. Ophthalmology 1986, 93:586-589. The KROC collaborative study group.
123. Kowluru R.A., Santos J.M., Mishra M. Epigenetic modifications and diabetic retinopathy. Biomed. Res. Int. 2013, 2013:635284.
124. Kumagai A.K. Glucose transport in brain and retina: implications in the management and complications of diabetes. Diabetes Metab. Res. Rev. 1999, 15:261-273.
125. Kusari J., Zhou S., Padillo E., Clarke K.G., Gil D.W. Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats. Invest. Ophthalmol. Vis. Sci. 2007, 48(11):5152-5159.
126. Kusari J., Zhou S.X., Padillo E., Clarke K.G., Gil D.W. Inhibition of vitreoretinal VEGF elevation and blood-retinal barrier breakdown in streptozotocin-induced diabetic rats by brimonidine. Invest. Ophthalmol. Vis. Sci. 2010, 51(2):1044-1051.
127. Kur J., Newman E.A., Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog. Retin. Eye Res. 2012, 31:377-406.
128. Lachin I., Genuth S., Nathan D., Zinman B., Rutledge B. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial - revisited. Diabetes 2008, 57:995-1001.
129. Lang G.E. Optical coherence tomography findings in diabetic retinopathy. Dev. Ophthalmol. 2007, 39:31-47.
130. Lang G.E., Berta A., Eldem B.M., Simader C., Sharp D., Holz F.G., Sutter F., Gerstner O., Mitchell P. Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study. Ophthalmology 2013, 120(10):2004-2012. RESTORE Extension Study Group.
131. Laursen J.V., Hoffmann S.S., Green A., Nybo M., Sjølie A.K., Grauslund J. Associations between diabetic retinopathy and plasma levels of high-sensitive C-reactive protein or von Willebrand factor in long-term type 1 diabetic patients. Curr. Eye Res. 2013, 38(1):174-179.
132. Leal E.C., Manivannan A., Hosoya K., Terasaki T., Cunha-Vaz J., Ambrosio A.F., Forrester J.V. Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2007, 48:5257-5265.
133. Leal E.C., Ambrósio A.F., Cunha-Vaz J. Nitric oxide synthase in retinal vascular diseases. Studies on Retinal and Choroidal Disorders; Oxidative Stress in Applied Basic Research and Clinical Practice 2012, 529-544. Springer Science and Business Media, LLC, New York. R.D. Stratton, W.W. Hauswirth, T.W. Gardner (Eds.).
134. Lecleire-Collet A., Audo I., Aout M., Girmens J.F., Sofroni R., Erginay A., Le Gargasson J.F., Mohand-Saïd S., Meas T., Guillausseau P.J., Vicaut E., Paques M., Massin P. Evaluation of retinal function and flicker light-induced retinal vascular response in normotensive patients with diabetes without retinopathy. Invest. Ophthalmol. Vis. Sci. 2011, 52(6):2861-2867.
135. Leslie R.D.G., Pyke D.A. Diabetic retinopathy in identical twins. Diabetes 1982, 31:19-21.
136. Li Z.Z., Lu X.Z., Liu J.B., Chen L. Serum retinol-binding protein 4 levels in patients with diabetic retinopathy. J. Int. Med. Res. 2010, 38(1):95-99.
137. Liu Y., Leo L.F., McGregor C., Grivitishvili A., Barnstable C.J., Tombran-Tink J. Pigment epithelium-derived factor (PEDF) peptide eye drops reduce inflammation, cell death and vascular leakage in diabetic retinopathy in Ins2(Akita) mice. Mol. Med. 2012, 18:1387-1401.
138. Lobo C.L., Berrnardes R.C., Santos F.J., Cunha-Vaz J.G. Mapping retinal fluorescein leakage with confocal scanning laser fluorometry of the human vitreous. Arch. Ophthalmol. 1999, 117:631-637.
139. Lobo C.L., Bernardes R.C., Figueira J.P., Faria de Abreu J.R., Cunha-Vaz J.G. Three-year follow-up of blood-retinal barrier and retinal thickness alterations in patients with type 2 diabetes mellitus and mild nonproliferative diabetic retinopathy. Arch. Ophthalmol. 2004, 122:211-217.
140. Lorenzi M., Gerhardinger C. Early cellular and molecular changes induced by diabetes in the retina. Diabetologia 2001, 44:791-804.
141. Ludovico J., Bernardes R., Pires I., Figueira J., Lobo C., Cunha-Vaz J.G. Alterations of retinal capillary blood flow in preclinical retinopathy in subjects with type 2 diabetes. Graefe's Arch. Clin. Exp. Ophthalmol. 2003, 41:181-186.
142. Luu C.D., Szental J.A., Lee S.Y., Lavanya R., Wong T.Y. Correlation between retinal oscillatory potentials and retinal vascular caliber in type 2 diabetes. Invest. Ophthalmol. Vis. Sci. 2010, 51(1):482-486.
143. Mark K.S., Burroughs A.R., Brown R.C., Huber J.D., Davis T.P. Nitric oxide mediates hypoxia-induced changes in paracellular permeability of cerebral microvasculature. Am. J. Physiol. Heart Circ. Physiol. 2004, 286(1):H174-H180.
144. Masmiquel L., Segura R.M., Mateo C., Calatayud M., Martí R., Mesa J., Simó R. Serum laminin as a marker of diabetic retinopathy development: a 4-year follow-up study. Am. J. Ophthalmol. 2000, 129(3):347-352.
145. Massin P., Girach A., Erginay A., Gaudric A. Optical coherence tomography: a key to the future management of patients with diabetic macular oedema. Acta Ophthalmol. Scand. 2006, 84(4):466-474.
146. Matsumoto K., Sera Y., Ueki Y., Inukai G., Niiro E., Miyake S. Comparison of serum concentrations of souble adhesion molecules in diabetic microangiopathy and macroangiopathy. Diabet. Med. 2002, 19(10):822-826.
147. Mayhan W.G. VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/cGMP-dependent pathway. Am. J. Physiol. 1999, 276(5 Pt 1):C1148-C1153.
148. Mei S., Cammalleri M., Azara D., Casini G., Bagnoli P., Dal Monte M. Mechanisms underlying somatostatin receptor 2 down-regulation of vascular endothelial growth factor expression in response to hypoxia in mouse retinal explants. J. Pathol. 2012, 226(3):519-533.
149. Metea M.R., Newman E.A. Signalling within the neurovascular unit in the mammalian retina. Exp. Physiol. 2007, 92:635-640.
150. Michaelson I.C. The mode of development of the vascular system of the retina with some observation for its significance for certain retinal diseases. Trans. Ophthalmol. Soc. UK 1948, 68:137-183.
151. Mori K., Gehlbach P., Ando A., McVey D., Wei L., Campochiaro P.A. Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor. Invest. Ophthalmol. Vis. Sci. 2002, 43(7):2428-2434.
152. Muni R.H., Kohly R.P., Lee E.Q., Manson J.E., Semba R.D., Schaumberg D.A. Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial. JAMA Ophthalmol. 2013, 131(4):514-521.
153. Murakami T., Felinski E.A., Antonetti D.A. Occludin phosphorylation and ubiquitination regulate tigh junction trafficking and vascular endothelial growth factor-induced permeability. K. Biol. Chem. 2009, 284:21036-21046.
154. Navaratna D., McGuire P.G., Menicucci G., Das A. Proteolytic degradation of VE-cadherin alters the blood-retinal barrier in diabetes. Diabetes 2007, 56:2380-2387.
155. Ng J.S., Bearse M.A., Schneck M.E., Barez S., Adams A.J. Local diabetic retinopathy prediction by multifocal ERG delays over 3 years. Invest. Ophthalmol. Vis. Sci. 2008, 49:1622-1628.
156. Nguyen Q.D., Shah S.M., Khwaja A.A., Channa R., Hatef E., Do D.V., Boyer D., Heier J.S., Abraham P., Thach A.B., Lit E.S., Foster B.S., Kruger E., Dugel P., Chang T., Das A., Ciulla T.A., Pollack J.S., Lim J.I., Eliot D., Campochiaro P.A. Two year outcomes of the Ranibizumab dor Edema of the mAcula in Diabetes (READ-2) study. Ophthalmology 2010, 117:2146-2151. for the READ-2 Study Group.
157. Nishikawa T., Edelstein D., Du X.L., Yamagishi S., Matsumura T., Kaneda Y., Yorek M.A., Beebe D., Oates P.J., Hammes H.P., Giardino I., Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000, 404:787-790.
158. Nowak M., Wielkoszynski T., Marek B., Kos-Kudla B., Swietochowska E., Sieminska L., Kajdaniuk D., Glogowska-Szelag J., Nowak K. Blood serum levels of vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) in diabetic retinopathy. Clin. Exp. Med. 2008, 8(3):159-164.
159. Nunes S., Pires I., Rosa A., Duarte L., Bernardes R., Cunha-Vaz J. Microaneurysm turnover is a biomarker for diabetic retinopathy progression to clinically significant macular edema: findings for type 2 diabetics with nonproliferative retinopathy. Ophthalmologica 2009, 223(5):292-297.
160. Nunes S., Ribeiro L., Lobo C., Cunha-Vaz J. Three different phenotypes of mild nonproliferative diabetic retinopathy with different risks for development of clinically significant macular edema. Invest. Ophthalmol. Vis. Sci. 2013, 54(7):4595-4604.
161. Omri S., Behar-Cohen F., Kozak Y., Sennlaub F., Verissimo L.M., Jonet L., Savoldelli M., Omri B., Crisanti P. Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: role of PKCζ in the Goto Kakizaki rat model. Am. J. Pathol. 2011, 179(2):942-953.
162. Otani T., Kishi S., Mauyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am. J. Ophthalmol. 1999, 127(6):688-693.
163. Parving H.H., Oxenbøll B., Svendsen P.A., Christiansen J.S., Andersen A.R. Early detection of patients at risk of developing diabetic nephropathy. Acta Endocrinon. (Copenh.) 1982, 100:550-555.
164. Pelletier E.M., Shim B., Ben-Joseph R., Caro J.J. Economic outcomes associated with microvascular complications of type 2 diabetes mellitus: results from a US claims data analysis. Pharmacoeconomics 2009, 27:479-490.
165. Pires I., Santos A.R., Nunes S., Lobo C., Cunha-Vaz J. Subclinical macular edema as a predictor of progression to clinically significant macular edema in diabetes type 2. Ophthalmologica 2013, 230(4):195-200.
166. Poulaki V., Qin W., Joussen A.M., Hurlbut P., Wiegand S.J., Rudge J., Yancopoulos G.D., Adamis A.P. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF. J. Clin. Invest 2002, 109(6):805-815.
167. Puliafito C.A., Hee M.R., Lin C.P., Reichel E., Schuman J.S., Duker J.S., Izatt J.A., Swanson E.A., Fujimoto J.G. Imaging of macular disease with optical coherence tomography. Ophthalmology 1995, 102(2):217-229.
168. Ribeiro L., Nunes S., Cunha-Vaz J. Microaneurysm turnover in the macula is a biomarker for the development of clinically significant macular edema in diabetes type 2. Curr. Biomark. Find. 2013, 3:11-15.
169. Ribeiro M.L., Nunes S., Cunha-Vaz J. Microaneurysm turnover at the macula predicts risk of development of clinically significant macular edema in persons with mild non-proliferative diabetic retinopathy. Diabetes Care 2013, 36:1254-1259.
170. Riva C.E., Logean E., Falsini B. Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina. Prog. Retin. Eye Res. 2005, 24:183-215.
171. Roy M.S., Janal M.N., Crosby J., Donnelly R. Inflammatory biomarkers and progression of diabetic retinopathy in African Americans with type 1 diabetes. Invest. Ophthalmol. Vis. Sci. 2013, 54(8):5471-5480.
172. Salman A.G., Mansour D.E., Swelem A.H., Al-Zawahary W.M., Radwan A.A. Pentosidine - a new biochemical marker in diabetic retinopathy. Ophthalmic Res. 2009, 42(2):96-98.
173. Sander B., Larsen M., Moldow B., Lund-Andersen H. Diabetic macular edema: passive and active transport of fluorescein through the blood-retina barrier. Invest. Ophthalmol. Vis. Sci. 2001, 42(2):433-438.
174. Santos A.R., Gomes S.C., Figueira J., Costa M., Lobo C., Cunha-Vaz J. Degree of decrease of central retinal thickness predicts the visual acuity response to intravitreal ranibizumab in diabetic macular edema. Ophthalmologica 2014, 231(1):16-22.
175. Sasongko M.B., Wong T.Y., Nguyen T.T., Kawasaki R., Jenkins A.J., Shaw J., Robinson C., Wang J.J. Serum apolipoproteins are associated with systemic and retinal microvascular function in people with diabetes. Diabetes 2012, 61(7):1785-1792.
176. Schlingemann R.O., van Hinsbergh V.W. Role of vascular permeability factor/vascular endothelial growth factor in eye disease. Br. J. Ophthalmol. 1997, 81:501-512.
177. Schulz K.F., Altman D.G., Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomized trials. Ann. Intern. Med. 2010, 152(11):726-732. for the CONSORT Group.
178. Shakib M., Cunha-Vaz J.G. Studies on the permeability of the blood-retinal barrier. IV. Junctional complexes of the retinal vessels and their role on their permeability. Exp. Eye Res. 1966, 5:229-234.
179. Shalchi Z., Sandhu H.S., Butt A.N., Smith S., Powrie J., Swaminathan R. Retina-specific mRNA in the assessment of diabetic retinopathy. Ann. N.Y. Acad. Sci. 2008, 117:253-257.
180. Shapiro C.R., Fagan A.M., Holtzmann D.M. Biomarkers of Alzheimer's disease. Neurobiol. Dis. 2009, 35:128-140.
181. Shen W., Li S., Chung S.H., Gillies M.C. Retinal vascular changes after glial disruption in rats. J. Neurosci. Res. 2010, 88(7):1485-1499.
182. Shen X., Xie B., Cheng Y., Jiao Q., Zhong Y. Effect of pigment epithelium derived factor on the expression of glutamine synthetase in early phase of experimental diabetic retinopathy. Ocul. Immunol. Inflamm. 2011, 19(4):246-254.
183. Silva K.C., Rosales M.A., Biswas S.K., Lopes de Faria J.B., Lopes de Faria J.M. Diabetic retinal neurodegeneration is associated with mitochondrial oxidative stress and is improved by an angiotensin receptor blocker in a model combining hypertension and diabetes. Diabetes 2009, 58(6):1382-1390.
184. Simó R., Masmiquel L., García-Pascual L., Burgos R., Mateo C., Segura R.M., Mesa J. Serum concentrations of laminin-P1 in diabetes mellitus: usefulness as an index of microangiopathy. Diabetes Res. Clin. Pract. 1996, 32(1-2):45-53.
185. Simó R., Carrasco E., García-Ramírez M., Hernández C. Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr. Diabetes Rev. 2006, 2:71-98.
186. Simó R., Hernandez C. Neurodegeneration is an early event in diabetic retinopathy: therapeutic implications. Br. J. Ophthalmol. 2012, 96:1285-1290. on behalf of the European Consortium for the Early Treatment of Diabetic Retinopathy.
187. Simó R., Hernández C. Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends Endocrinol. Metab. 2013, 25:23-33.
188. Simó-Servat O., Hernández C., Simó R. Genetics in diabetic retinopathy: current concepts and new insights. Curr. Genomics 2013, 14:289-299.
189. Soedamah-Muthu S.S., Chaturvedi N., Schalkwijk C.G., Stehouwer C.D., Ebeling P., Fuller J.H. Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macrovascular complications in Type 1 diabetic patients. J. Diabetes Complicat. 2006, 20(3):188-195. EURODIAB Prospective Complications Study Group.
190. Soliman W., Sander B., Hasler P.W., Larsen M. Correlation between intraretinal changes in diabetic macular oedema seen in fluorescein angiography and optical coherence tomography. Acta Ophthalmol. 2008, 86(1):34-39.
191. Sng C.C., Cheung C.Y., Man R.E., Wong W., Lavanya R., Mitchell P., Aung T., Wong T.Y. Influence of diabetes on macular thickness measured using optical coherence tomography: the Singapore Indian Eye Study. Eye 2012, 26(5):690-698.
192. Snyderman R., Williams R.S. Prospective medicine: the next health care transformation. Acad. Med. 2003, 78(11):1079-1084.
193. Stem M.S., Gardner T.W. Neurodegeneration in the pathogenesis of diabetic retinopathy: molecular mechanisms and therapeutic implications. Curr. Med. Chem. 2013, 20(26):3241-3250.
194. Stratton I.M., Kohner E.M., Aldington S.J., Turner R.C., Holman R.R., Manley S.E., Matthews D.R. UKPDS 50: risk factors for incidence and progression of retinopathy in type II diabetes over 6 years from diagnosis. Diabetologia 2001, 44:156-163.
195. Takebayashi K., Suetsugu M., Wakabayashi S., Aso Y., Inukai T. Retinol binding protein-4 levels and clinical features of type 2 diabetes patients. J. Clin. Endocrinol. Metab. 2007, 92(7):2712-2719.
196. Tang J., Kern T.S. Inflammation in diabetic retinopathy. Prog. Retin. Eye Res. 2011, 30:343-358.
197. Tang Z.H., Fang Z., Zhou L. Human genetics of diabetic vascular complications. J. Genet. 2013, 92(3):677-694.
198. Tevak Z., Kondrativich M., Mansfield E. US FDA and personalized medicine: invitro diagnostic regulatory perspective. Pers. Med. 2010, 7:517-530.
199. Tso M.O.M., Cunha-Vaz J.G., Shih C.Y., Jones C.W. Clinicopathologic study of blood-retinal barriers in experimental diabetes mellitus. Arch. Ophthalmol. 1980, 98:2032-2040.
200. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus. Arch. Ophthamol. 2004, 122:1631-1640. UK Prospective Diabetes Study (UKPDS) Group.
201. Valone J.A., McNeel J.W., Franks E.P. Unilateral proliferative diabetic retinopathy. I. Initial Findings. Arch. Ophthalmol. 1981, 99:1357-1361.
202. VanGuilder H.D., Brucklacher R.M., Patel K., Ellis R.W., Freeman W.M., Barber A.J. Diabetes downregulates presynaptic proteins and reduces basal synapsin 1 phosphotylation in rat retina. Eur. J. Neurosci. 2008, 28(1):1-11.
203. Van Gueest R.J., Klaassen I., Vogles I.M., Van Noorden C.J., Schlingemann R.O. Differential TGF-{beta} signaling in retinal vascular cells: a role in diabetic retinopathy?. Invest. Ophthalmol. Vis. Sci. 2010, 51:1857-1865.
204. Van Hecke M.V., Dekke J.M., Nijpels G., Moll A.C., Heine R.J., Bouter L.M., Polak B.C., Stenhouwer C.D. Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study. Diabetologia 2005, 48(7):1300-1306.
205. Van Hecke M.V., Dekker J.M., Njpels G., Teerlink T., Jakobs C., Stolk R.P., Heine R.J., Bouter L.M., Polak B.C., Stehouwer C.D. Homocysteina, S-adenosylmethionine and S-adenosylhomocysteine are associated with retinal microvascular abnormalities: the Hoorn Study. Clin. Sci. (Lond) 2008, 114(7):479-487.
206. Waltman S.R., Krupin T., Hanish S. Alterations of the blood-retinal barrier in experimental diabetes mellitus. Arch. Ophthamol. 1978, 96:878-879.
207. Wang J., Xu X., Elliott M.H., Zhu M., Le Y.Z. Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes 2010, 59(9):2297-2305.
208. Warpeha K.M., Chakravarthy U. Molecular genetics of microvascular disease in diabetic retinopathy. Eye 2003, 17:305-311.
209. Wautier M.P., Massin P., Guillausseau P.J., Hujiberts M., Levy B., Boulanger E., Laloi-Michelin M., Wautier J.L. N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients. Diabetes Metab. 2003, 29(1):44-52.
210. Wilkinson-Berka J.L., Tan G., Jaworski K., Miller A.G. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology. Circ. Res. 2009, 104:124-133.
211. Wilson S.H., Davis M.I., Caballero S., Grant M.B. Modulation of retinal endothelial cell behaviour by insulin-like growth factor I and somatostatin analogues: implications for diabetic retinopathy. Growth Horm. IGF Res. 2001, 11(Suppl. A):S53-S59.
212. Wise G.N. Retinal neovascularization. Trans. Am. Ophthalmol. Soc. 1956, 54:729-826.
213. Wong K. Defining diabetic retinopathy severity. Diabetic Retinopathy 2010, 105-120. Springer Science+Business Media, LLC, New York. D.J. Browning (Ed.).
214. Wurm A., Pannicke T., Iandiev I., Francke M., Hollborn M., Wiedemann P., Reichenbach A., Osborne N.N., Bringmann A. Purinergic signaling involved in Müller cell function in the mammalian retina. Prog. Retin. Eye Res. 2011, 30(5):324-342.
215. Xu H.Z., Le Y.Z. Significance of outer blood-retina barrier breakdown in diabetes and ischemia. Invest. Ophthalmol. Vis. Sci. 2011, 52:2160-2164.
216. Yang C.S., Cheng C.Y., Lee F.L., Hsu W.M., Liu J.H. Quantitative assessment of retinal thickness in diabetic patients with and without clinically significant macular edema using optical coherence tomography. Acta Ophthalmol. Scand. 2001, 79(3):266-270.
217. Yang J., Duh E.J., Caldwell R.B., Behzadian M.A. Antipermeability function of PEDF involves vlockade of the MAP kinase/GSK/beta-catenin signaling pathway and uPAR expression. Invest. Ophthalmol. Vis. Sci. 2010, 51:3273-3280.
218. Yau J.W., Rogers S.L., Kawasaki R., Lamoureux E.L., Kowalski J.W., Bek T., Chen S.J., Dekker J.M., Fletcher A., Grauslund J., Haffner S., Hamman R.F., Ikram M.K., Kayama T., Klein B.E., Klein R., Krishnaiah S., Mayurasakorn K., O'Hare J.P., Orchard T.J., Porta M., Rema M., Roy M.S., Sharma T., Shaw J., Taylor H., Tielsch J.M., Varma R., Wang J.J., Wang N., West S., Xu L., Yasuda M., Zhang X., Mitchell P., Wong T.Y. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012, 35:556-564. Meta-Analysis for Eye Disease (META-EYE) Study Group.
219. Yoshida Y., Yamagishi S., Matsui T., Jinnouchi Y., Fukami K., Imaizumi T., Yamakawa R. Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy. Diabetes Metab. Res. Rev. 2009, 25(7):678-686.
220. Yoshizawa M., Nagai Y., Ohsawa K., Ohta M., Yamashita H., Hisada A., Miyamoto I., Miura K., Takamura T., Kobayashi K. Elevated serum levels of soluble vascular cell adhesion molecule-1 in NIDDM patients with proliferative diabetic retinopathy. Diabetes Res. Clin. Pract. 1998, 42(1):65-70.
221. Zeeuw D. Microalbuminuria: a risk factor for cardiovascular morbidity and mortality in diabetes. A target treatment. Int. Diabetes Monit. 2007, 19(2):12-16.
222. Zhang S.X., Wang J.J., Gao G., Parke K., Ma J.X. Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J. Mol. Endocrinol. 2006, 37(1):1-12.
223. Zheng L., Du Y., Miller C., Gubitosi-Klug R.A., Ball S., Berkowitz B.A., Kern T.S. Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes. Diabetologia 2007, 50(9):1987-1996.
224. Zhong Q., Kowluru R.A. Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy. Diabetes 2011, 60(4):1304-1313.
225. Zhong Y., Li J., Chen Y., Wang J.J., Ratan R., Zhang S.X. Activation of endoplasmic reticulum stress by hyperglycemia is essential for Müller cell-derived inflammatory cytokine production in diabetes. Diabetes 2012, 61(2):492-504.
226. Zong H., Ward M., Madden A., Yong P.H., Limb G.A., Curtis T.M., Stitt A.W. Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE). Diabetologia 2010, 53(12):2656-2666.