Targeting neovascularization in ischemic retinopathy: Recent advances

Expert Review of Ophthalmology

Volumn 8, Issue 3, 2013, Pages 267-286

  Al Shabrawey, Mohamed ^a,b   Elsherbiny, Mohamed ^a,c   Nussbaum, Julian ^b   Othman, Amira ^c   Megyerdi, Sylvia ^a   Tawfik, Amany ^b  

^a AUGUSTA UNIVERSITY   (United States)

^b MEDICAL COLLEGE OF GEORGIA   (United States)

^c MANSOURA UNIVERSITY   (Egypt)

Author keywords

inflammation; lipoxygenase; oxidative stress; PEDF; PPAR; retinal neovascularization; retinopathy; VEGF

Indexed keywords

ACETYLSALICYLIC ACID; ADENOVIRUS VECTOR; AFLIBERCEPT; ALPHA TOCOPHEROL; ANGIOSTATIN; BEVACIZUMAB; CATALASE; CORTICOSTEROID; DOXYCYCLINE; ERYTHROPOIETIN; IBUPROFEN; LISINOPRIL; LUTEOLIN; MINOCYCLINE; NEPAFENAC; PEGAPTANIB; PIGMENT EPITHELIUM DERIVED FACTOR; PRINOMASTAT; RANIBIZUMAB; RECOMBINANT ERYTHROPOIETIN; RUBOXISTAURIN; SALICYLATE SODIUM; SEGLITIDE; SIRNA 027; SUPEROXIDE DISMUTASE; TRIAMCINOLONE ACETONIDE; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; XANTHOPHYLL;

ANTIOXIDANT ACTIVITY; ARTERIAL THROMBOEMBOLISM; BLEEDING; BLOOD RETINA BARRIER; CATARACT; CELL INTERACTION; CENTRAL RETINA VEIN OCCLUSION; CONJUNCTIVAL HEMORRHAGE; DIABETIC MACULAR EDEMA; DIABETIC RETINOPATHY; DIGESTIVE SYSTEM PERFORATION; DRUG EFFECT; DRUG HALF LIFE; DRUG METABOLISM; DRUG TARGETING; ENDOPHTHALMITIS; ENDOTHELIUM CELL; GLIA CELL; HUMAN; HYPERTENSIVE CRISIS; IMMUNE RESPONSE; INFLAMMATION; INTRAOCULAR HYPERTENSION; LASER COAGULATION; LIPID METABOLISM; LOW LEVEL LASER THERAPY; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PIGMENT EPITHELIUM; PROTEIN EXPRESSION; RETINA DETACHMENT; RETINA ISCHEMIA; RETINA MACULA AGE RELATED DEGENERATION; RETINA NEOVASCULARIZATION; RETINITIS; RETROLENTAL FIBROPLASIA; REVIEW; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SUBRETINAL NEOVASCULARIZATION; SYSTEMIC DISEASE; VITRECTOMY;

EID: 84879670618     PISSN: 17469899     EISSN: 17469902     Source Type: Journal    
DOI: 10.1586/eop.13.17     Document Type: Review

References (247)

1. Buch H, Vinding T, Nielsen NV. Prevalence and causes of visual impairment according to World Health Organization and United States criteria in an aged, urban Scandinavian population: the Copenhagen City Eye Study. Ophthalmology 108(12), 2347-2357 (2001).
2. Congdon N, O'Colmain B, Klaver CC et al.; Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch. Ophthalmol. 122(4), 477-485 (2004).
3. Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J; Vision Health Cost-Effectiveness Study Group. Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments. Arch. Ophthalmol. 127(4), 533-540 (2009).
4. Saaddine JB, Honeycutt AA, Narayan KM, Zhang X, Klein R, Boyle JP. Projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus: United States, 2005-2050. Arch. Ophthalmol. 126(12), 1740-1747 (2008).
5. Folkman J, Ingber D. Inhibition of angiogenesis. Semin. Cancer Biol. 3(2), 89-96 (1992).
6. Folkman J, Shing Y. Angiogenesis. J. Biol. Chem. 267(16), 10931-10934 (1992).
7. Cao Y. Endogenous angiogenesis inhibitors and their therapeutic implications. Int. J. Biochem. Cell Biol. 33(4), 357-369 (2001).
8. Gao G, Li Y, Zhang D, Gee S, Crosson C, Ma J. Unbalanced expression of VEGF and PEDF in ischemia-induced retinal neovascularization. FEBS Lett. 489(2-3), 270-276 (2001).
9. Gao G, Ma J. Tipping the balance for angiogenic disorders. Drug Discov. Today 7(3), 171-172 (2002).
10. Ma JX, Zhang SX, Wang JJ. Downregulation of angiogenic inhibitors: a potential pathogenic mechanism for diabetic complications. Curr. Diabetes Rev. 1(2), 183-196 (2005).
11. Battegay EJ. Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J. Mol. Med. 73(7), 333-346 (1995).
12. Kim J, Kim CS, Lee YM, Jo K, Shin SD, Kim JS. Methylglyoxal induces hyperpermeability of the blood-retinal barrier via the loss of tight junction proteins and the activation of matrix metalloproteinases. Graefes Arch. Clin. Exp. Ophthalmol. 250(5), 691-697 (2012).
13. Peng S, Gan G, Rao VS, Adelman RA, Rizzolo LJ. Effects of proinflammatory cytokines on the claudin-19 rich tight junctions of human retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 53(8), 5016-5028 (2012).
14. Armulik A, Genové G, Mäe M et al. Pericytes regulate the blood-brain barrier. Nature 468(7323), 557-561 (2010).
15. Hosoya K, Fujita K, Tachikawa M. Involvement of reduced folate carrier 1 in the inner blood-retinal barrier transport of methyltetrahydrofolate. Drug Metab. Pharmacokinet. 23(4), 285-292 (2008).
16. Runkle EA, Antonetti DA. The blood-retinal barrier: structure and functional significance. Methods Mol. Biol. 686, 133-148 (2011).
17. Ejaz S, Chekarova I, Ejaz A, Sohail A, Lim CW. Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy. Diabetes. Obes. Metab. 10(1), 53-63 (2008).
18. Asahara T, Murohara T, Sullivan A et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302), 964-967 (1997).
19. Patan S. Vasculogenesis and angiogenesis. Cancer Treat. Res. 117, 3-32 (2004).
20. Hughes S, Yang H, Chan-Ling T. Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis. Invest. Ophthalmol. Vis. Sci. 41(5), 1217-1228 (2000).
21. Chan-Ling T, McLeod DS, Hughes S et al. Astrocyte-endothelial cell relationships during human retinal vascular development. Invest. Ophthalmol. Vis. Sci. 45(6), 2020-2032 (2004).
22. Flower RW, McLeod DS, Lutty GA, Goldberg B, Wajer SD. Postnatal retinal vascular development of the puppy. Invest. Ophthalmol. Vis. Sci. 26(7), 957-968 (1985).
23. Grant MB, May WS, Caballero S et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat. Med. 8(6), 607-612 (2002).
24. Abu El-Asrar AM, Nawaz MI, Kangave D, Siddiquei MM, Ola MS, Opdenakker G. Angiogenesis regulatory factors in the vitreous from patients with proliferative diabetic retinopathy. Acta Diabetol. doi:10.1007/s00592-011-0330-9 (2011) (Epub ahead of print).
25. Abu El-Asrar AM, Struyf S, Opdenakker G, Van Damme J, Geboes K. Expression of stem cell factor/c-kit signaling pathway components in diabetic fibrovascular epiretinal membranes. Mol. Vis. 16, 1098-1107 (2010).
26. Sengupta N, Caballero S, Mames RN, Timmers AM, Saban D, Grant MB. Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors. Invest. Ophthalmol. Vis. Sci. 46(1), 343-348 (2005).
27. Ash JD, Overbeek PA. Lens-specific VEGF-A expression induces angioblast migration and proliferation and stimulates angiogenic remodeling. Dev. Biol. 223(2), 383-398 (2000).
28. Sengupta N, Caballero S, Mames RN, Butler JM, Scott EW, Grant MB. The role of adult bone marrow-derived stem cells in choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 44(11), 4908-4913 (2003).
29. Tarr JM, Kaul K, Wolanska K, Kohner EM, Chibber R. Retinopathy in diabetes. Adv. Exp. Med. Biol. 771, 88-106 (2012).
30. Antonetti DA, Barber AJ, Hollinger LA, Wolpert EB, Gardner TW. Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechanism for vascular permeability in diabetic retinopathy and tumors. J. Biol. Chem. 274(33), 23463-23467 (1999).
31. Antonetti DA, Lieth E, Barber AJ, Gardner TW. Molecular mechanisms of vascular permeability in diabetic retinopathy. Semin. Ophthalmol. 14(4), 240-248 (1999).
32. Leal EC, Manivannan A, Hosoya K et al. Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 48(11), 5257-5265 (2007).
33. Di Fiore JM, Kaffashi F, Loparo K et al. The relationship between patterns of intermittent hypoxia and retinopathy of prematurity in preterm infants. Pediatr. Res. 72(6), 606-612 (2012).
34. Grimm C, Willmann G. Hypoxia in the eye: a two-sided coin. High Alt. Med. Biol. 13(3), 169-175 (2012).
35. Steinle JJ. Retinal endothelial cell apoptosis. Apoptosis 17(12), 1258-1260 (2012).
36. Li SY, Fu ZJ, Lo AC. Hypoxia-induced oxidative stress in ischemic retinopathy. Oxid. Med. Cell. Longev. 2012, 426769 (2012).
37. Arden GB, Sivaprasad S. The pathogenesis of early retinal changes of diabetic retinopathy. Doc. Ophthalmol. 124(1), 15-26 (2012).
38. Reichenbach A, Wurm A, Pannicke T, Iandiev I, Wiedemann P, Bringmann A. Müller cells as players in retinal degeneration and edema. Graefes Arch. Clin. Exp. Ophthalmol. 245(5), 627-636 (2007).
39. Klaassen I, Hughes JM, Vogels IM, Schalkwijk CG, Van Noorden CJ, Schlingemann RO. Altered expression of genes related to blood-retina barrier disruption in streptozotocin-induced diabetes. Exp. Eye Res. 89(1), 4-15 (2009).
40. Kubota Y, Suda T. Feedback mechanism between blood vessels and astrocytes in retinal vascular development. Trends Cardiovasc. Med. 19(2), 38-43 (2009).
41. Tretiach M, Madigan MC, Wen L, Gillies MC. Effect of Müller cell co-culture on in vitro permeability of bovine retinal vascular endothelium in normoxic and hypoxic conditions. Neurosci. Lett. 378(3), 160-165 (2005).
42. Eichler W, Yafai Y, Keller T, Wiedemann P, Reichenbach A. PEDF derived from glial Müller cells: a possible regulator of retinal angiogenesis. Exp. Cell Res. 299(1), 68-78 (2004).
43. Duh EJ, Yang HS, Suzuma I et al. Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Invest. Ophthalmol. Vis. Sci. 43(3), 821-829 (2002).
44. Coorey NJ, Shen W, Chung SH, Zhu L, Gillies MC. The role of glia in retinal vascular disease. Clin. Exp. Optom. 95(3), 266-281 (2012).
45. Robaszkiewicz J, Chmielewska K, Figurska M, Wierzbowska J, Stankiewicz A. Müller glial cells - the mediators of vascular disorders with vitreomacular interface pathology in diabetic maculopathy. Klin. Oczna. 112(10-12), 328-332 (2010).
46. Michaelson IC, Herz N, Lewkowitz E, Kertesz D. Effect of increased oxygen on the development of the retinal vessels; an experimental study. Br. J. Ophthalmol. 38(10), 577-587 (1954).
47. Aiello LP, Avery RL, Arrigg PG et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med. 331(22), 1480-1487 (1994).
48. Adamis AP, Miller JW, Bernal MT et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am. J. Ophthalmol. 118(4), 445-450 (1994).
49. Miller JW, Adamis AP, Shima DT et al. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am. J. Pathol. 145(3), 574-584 (1994).
50. Aiello LP, Northrup JM, Keyt BA, Takagi H, Iwamoto MA. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch. Ophthalmol. 113(12), 1538-1544 (1995).
51. Aiello LP, Pierce EA, Foley ED et al. 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 (1995).
52. Krzystolik MG, Afshari MA, Adamis AP et al. Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch. Ophthalmol. 120(3), 338-346 (2002).
53. Tolentino MJ, Miller JW, Gragoudas ES, Chatzistefanou K, Ferrara N, Adamis AP. Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate. Arch. Ophthalmol. 114(8), 964-970 (1996).
54. Tolentino MJ, Miller JW, Gragoudas ES et al. Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology 103(11), 1820-1828 (1996).
55. Lashkari K, Hirose T, Yazdany J, McMeel JW, Kazlauskas A, Rahimi N. Vascular endothelial growth factor and hepatocyte growth factor levels are differentially elevated in patients with advanced retinopathy of prematurity. Am. J. Pathol. 156(4), 1337-1344 (2000).
56. Funatsu H, Yamashita H, Ikeda T, Nakanishi Y, Kitano S, Hori S. Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders. Am. J. Ophthalmol. 133(4), 537-543 (2002).
57. Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 110(9), 1690-1696 (2003).
58. Funatsu H, Yamashita H, Sakata K et al. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology 112(5), 806-816 (2005).
59. Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am. J. Ophthalmol. 133(1), 70-77 (2002).
60. Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong PT. Increased expression of angiogenic growth factors in age-related maculopathy. Br. J. Ophthalmol. 81(2), 154-162 (1997).
61. Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR. Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest. Ophthalmol. Vis. Sci. 37(5), 855-868 (1996).
62. Frank RN, Amin RH, Eliott D, Puklin JE, Abrams GW. Basic fibroblast growth factor and vascular endothelial growth factor are present in epiretinal and choroidal neovascular membranes. Am. J. Ophthalmol. 122(3), 393-403 (1996).
63. Grossniklaus HE, Ling JX, Wallace TM et al. Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol. Vis. 8, 119-126 (2002).
64. Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW. The vascular endothelial growth factor family of polypeptides. J. Cell. Biochem. 47(3), 211-218 (1991).
65. Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LE. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc. Natl Acad. Sci. USA 92(3), 905-909 (1995).
66. Dorey CK, Aouididi S, Reynaud X, Dvorak HF, Brown LF. Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat. Arch. Ophthalmol. 114(10), 1210-1217 (1996).
67. Pe'er J, Shweiki D, Itin A, Hemo I, Gnessin H, Keshet E. Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab. Invest. 72(6), 638-645 (1995).
68. Lu M, Amano S, Miyamoto K et al. Insulin-induced vascular endothelial growth factor expression in retina. Invest. Ophthalmol. Vis. Sci. 40(13), 3281-3286 (1999).
69. Ray D, Mishra M, Ralph S, Read I, Davies R, Brenchley P. Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes. Diabetes 53(3), 861-864 (2004).
70. Braun L, Kardon T, Reisz-Porszasz ZS, Banhegyi G, Mandl J. The regulation of the induction of vascular endothelial growth factor at the onset of diabetes in spontaneously diabetic rats. Life Sci. 69(21), 2533-2542 (2001).
71. Qaum T, Xu Q, Joussen AM et al. VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest. Ophthalmol. Vis. Sci. 42(10), 2408-2413 (2001).
72. Murata T, Nakagawa K, Khalil A, Ishibashi T, Inomata H, Sueishi K. The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas. Lab. Invest. 74(4), 819-825 (1996).
73. Hu J, Song X, He YQ et al. Heparanase and vascular endothelial growth factor expression is increased in hypoxia-induced retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 53(11), 6810-6817 (2012).
74. Ishida S, Usui T, Yamashiro K et al. VEGF164 is proinflammatory in the diabetic retina. Invest. Ophthalmol. Vis. Sci. 44(5), 2155-2162 (2003).
75. Kinose F, Roscilli G, Lamartina S et al. Inhibition of retinal and choroidal neovascularization by a novel KDR kinase inhibitor. Mol. Vis. 11, 366-373 (2005).
76. McLeod DS, Taomoto M, Otsuji T, Green WR, Sunness JS, Lutty GA. Quantifying changes in RPE and choroidal vasculature in eyes with age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 43(6), 1986-1993 (2002).
77. Krantz SB. Erythropoietin. Blood 77(3), 419-434 (1991).
78. Erbayraktar S, Yilmaz O, Gökmen N, Brines M. Erythropoietin is a multifunctional tissue-protective cytokine. Curr. Hematol. Rep. 2(6), 465-470 (2003).
79. Carlini RG, Reyes AA, Rothstein M. Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int. 47(3), 740-745 (1995).
80. Alvarez Arroyo MV, Castilla MA, González Pacheco FR et al. Role of vascular endothelial growth factor on erythropoietin- related endothelial cell proliferation. J. Am. Soc. Nephrol. 9(11), 1998-2004 (1998).
81. Chong ZZ, Kang JQ, Maiese K. Angiogenesis and plasticity: role of erythropoietin in vascular systems. J. Hematother. Stem Cell Res. 11(6), 863-871 (2002).
82. Grimm C, Wenzel A, Groszer M et al. HIF-1-induced erythropoietin in the hypoxic retina protects against lightinduced retinal degeneration. Nat. Med. 8(7), 718-724 (2002).
83. Morita M, Ohneda O, Yamashita T et al. HLF/HIF-2α is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J. 22(5), 1134-1146 (2003).
84. Watanabe D, Suzuma K, Matsui S et al. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N. Engl. J. Med. 353(8), 782-792 (2005).
85. Maiese K, Li F, Chong ZZ. New avenues of exploration for erythropoietin. JAMA 293(1), 90-95 (2005).
86. Aiello LP. Angiogenic pathways in diabetic retinopathy. N. Engl. J. Med. 353(8), 839-841 (2005).
87. Mitsuhashi J, Morikawa S, Shimizu K, Ezaki T, Yasuda Y, Hori S. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocininduced diabetic rats. Exp. Eye Res. 106, 64-73 (2013).
88. Delafontaine P, Song YH, Li Y. Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler. Thromb. Vasc. Biol. 24(3), 435-444 (2004).
89. Lambooij AC, van Wely KH, LindenberghKortleve DJ, Kuijpers RW, Kliffen M, Mooy CM. Insulin-like growth factor-I and its receptor in neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 44(5), 2192-2198 (2003).
90. Hellström A, Carlsson B, Niklasson A et al. IGF-I is critical for normal vascularization of the human retina. J. Clin. Endocrinol. Metab. 87(7), 3413-3416 (2002).
91. Hellstrom A, Perruzzi C, Ju M et al. 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 (2001).
92. Smith LE. Pathogenesis of retinopathy of prematurity. Growth Horm. IGF Res. 14(Suppl. A), S140-S144 (2004).
93. Ruberte J, Ayuso E, Navarro M et al. Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease. J. Clin. Invest. 113(8), 1149-1157 (2004).
94. Nourhaghighi N, Teichert-Kuliszewska K, Davis J, Stewart DJ, Nag S. Altered expression of angiopoietins during blood-brain barrier breakdown and angiogenesis. Lab. Invest. 83(8), 1211-1222 (2003).
95. Valable S, Montaner J, Bellail A et al. VEGF-induced BBB permeability is associated with an MMP-9 activity increase in cerebral ischemia: both effects decreased by Ang-1. J. Cereb. Blood Flow Metab. 25(11), 1491-1504 (2005).
96. Nambu H, Nambu R, Oshima Y et al. Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier. Gene Ther. 11(10), 865-873 (2004).
97. Hackett SF, Wiegand S, Yancopoulos G, Campochiaro PA. Angiopoietin-2 plays an important role in retinal angiogenesis. J. Cell. Physiol. 192(2), 182-187 (2002).
98. Das A, Fanslow W, Cerretti D, Warren E, Talarico N, McGuire P. Angiopoietin/Tek interactions regulate MMP-9 expression and retinal neovascularization. Lab. Invest. 83(11), 1637-1645 (2003).
99. Oshima Y, Deering T, Oshima S et al. Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor. J. Cell. Physiol. 199(3), 412-417 (2004).
100. Umeda N, Ozaki H, Hayashi H, Miyajima- Uchida H, Oshima K. Colocalization of Tie2, angiopoietin 2 and vascular endothelial growth factor in fibrovascular membrane from patients with retinopathy of prematurity. Ophthalmic Res. 35(4), 217-223 (2003).
101. Das A, McGuire PG. Retinal and choroidal angiogenesis: pathophysiology and strategies for inhibition. Prog. Retin. Eye Res. 22(6), 721-748 (2003).
102. Mohr S, Xi X, Tang J, Kern TS. Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients. Diabetes 51(4), 1172-1179 (2002).
103. Anderson RE, Rapp LM, Wiegand RD. Lipid peroxidation and retinal degeneration. Curr. Eye Res. 3(1), 223-227 (1984).
104. Kowluru RA. Effect of reinstitution of good glycemic control on retinal oxidative stress and nitrative stress in diabetic rats. Diabetes 52(3), 818-823 (2003).
105. Kowluru RA, Atasi L, Ho YS. Role of mitochondrial superoxide dismutase in the development of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 47(4), 1594-1599 (2006).
106. Al-Shabrawey M, Bartoli M, El-Remessy AB et al. Role of NADPH oxidase and Stat3 in statin-mediated protection against diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 49(7), 3231-3238 (2008).
107. Al-Shabrawey M, Bartoli M, El-Remessy AB et al. Inhibition of NAD(P)H oxidase activity blocks vascular endothelial growth factor overexpression and neovascularization during ischemic retinopathy. Am. J. Pathol. 167(2), 599-607 (2005).
108. Al-Shabrawey M, Rojas M, Sanders T et al. Role of NADPH oxidase in retinal vascular inflammation. Invest. Ophthalmol. Vis. Sci. 49(7), 3239-3244 (2008).
109. Miwa K, Nakamura J, Hamada Y et al. The role of polyol pathway in glucose-induced apoptosis of cultured retinal pericytes. Diabetes Res. Clin. Pract. 60(1), 1-9 (2003).
110. Al-Shabrawey M, El-Remessy A, Gu X et al. Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase. Mol. Vis. 9, 549-558 (2003).
111. Stitt AW. The role of advanced glycation in the pathogenesis of diabetic retinopathy. Exp. Mol. Pathol. 75(1), 95-108 (2003).
112. Lelkes PI, Hahn KL, Sukovich DA, Karmiol S, Schmidt DH. On the possible role of reactive oxygen species in angiogenesis. Adv. Exp. Med. Biol. 454, 295-310 (1998).
113. Buhimschi IA, Buhimschi CS, Weiner CP. Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation. Am. J. Obstet. Gynecol. 188(1), 203-208 (2003).
114. Saito Y, Uppal A, Byfield G, Budd S, Hartnett ME. Activated NAD(P)H oxidase from supplemental oxygen induces neovascularization independent of VEGF in retinopathy of prematurity model. Invest. Ophthalmol. Vis. Sci. 49(4), 1591-1598 (2008).
115. Ushio-Fukai M. Redox signaling in angiogenesis: role of NADPH oxidase. Cardiovasc. Res. 71(2), 226-235 (2006).
116. Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett. 266(1), 37-52 (2008).
117. Tawfik A, Sanders T, Kahook K, Akeel S, Elmarakby A, Al-Shabrawey M. Suppression of retinal peroxisome proliferatoractivated receptor γ in experimental diabetes and oxygen-induced retinopathy: role of NADPH oxidase. Invest. Ophthalmol. Vis. Sci. 50(2), 878-884 (2009).
118. Jang DS, Lee YM, Jeong IH, Kim JS. Constituents of the flowers of Platycodon grandiflorum with inhibitory activity on advanced glycation end products and rat lens aldose reductase in vitro. Arch. Pharm. Res. 33(6), 875-880 (2010).
119. Williams RJ, Spencer JP, Rice-Evans C. Flavonoids: antioxidants or signaling molecules? Free Radic. Biol. Med. 36(7), 838-849 (2004).
120. Ansó E, Zuazo A, Irigoyen M, Urdaci MC, Rouzaut A, Martínez-Irujo JJ. Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism. Biochem. Pharmacol. 79(11), 1600-1609 (2010).
121. Park SW, Cho CS, Jun HO et al. Antiangiogenic effect of luteolin on retinal neovascularization via blockade of reactive oxygen species production. Invest. Ophthalmol. Vis. Sci. 53(12), 7718-7726 (2012).
122. Akeel S, El-Awady A, Hussein K et al. Recombinant bone morphogenetic protein-2 induces up-regulation of vascular endothelial growth factor and interleukin 6 in human pre-osteoblasts: role of reactive oxygen species. Arch. Oral Biol. 57(5), 445-452 (2012).
123. Dong A, Shen J, Krause M et al. Superoxide dismutase 1 protects retinal cells from oxidative damage. J. Cell. Physiol. 208(3), 516-526 (2006).
124. Imamura Y, Noda S, Hashizume K et al. Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc. Natl Acad. Sci. USA 103(30), 11282-11287 (2006).
125. Dong A, Xie B, Shen J et al. Oxidative stress promotes ocular neovascularization. J. Cell. Physiol. 219(3), 544-552 (2009).
126. Cao Y, Cao R. Angiogenesis inhibited by drinking tea. Nature 398(6726), 381 (1999).
127. Wang D, Wang H, Brown J et al. CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J. Exp. Med. 203(4), 941-951 (2006).
128. Nie D, Hillman GG, Geddes T et al. Platelet-type 12-lipoxygenase in a human prostate carcinoma stimulates angiogenesis and tumor growth. Cancer Res. 58(18), 4047-4051 (1998).
129. Tang DG, Renaud C, Stojakovic S, Diglio CA, Porter A, Honn KV. 12(S)-HETE is a mitogenic factor for microvascular endothelial cells: its potential role in angiogenesis. Biochem. Biophys. Res. Commun. 211(2), 462-468 (1995).
130. Li Z, He T, Du K et al. Overexpression of 15-lipoxygenase-1 in oxygen-induced ischemic retinopathy inhibits retinal neovascularization via downregulation of vascular endothelial growth factor-A expression. Mol. Vis. 18, 2847-2859 (2012).
131. Yan Y, He T, Shen Y et al. Adenoviral 15-lipoxygenase-1 gene transfer inhibits hypoxia-induced proliferation of retinal microvascular endothelial cells in vitro. Int. J. Ophthalmol. 5(5), 562-569 (2012).
132. Connor KM, SanGiovanni JP, Lofqvist C et al. Increased dietary intake of ω3polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat. Med. 13(7), 868-873 (2007).
133. Sapieha P, Stahl A, Chen J et al. 5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of ω-3 polyunsaturated fatty acids. Sci. Transl. Med. 3(69), 69ra12 (2011).
134. Al-Shabrawey M, Mussell R, Kahook K et al. Increased expression and activity of 12-lipoxygenase in oxygen-induced ischemic retinopathy and proliferative diabetic retinopathy: implications in retinal neovascularization. Diabetes 60(2), 614-624 (2011).
135. Othman A, Ahmad S, Megyerdi S et al. 12/15-lipoxygenase-derived lipid metabolites induce retinal endothelial cell barrier dysfunction: contribution of NADPH oxidase. PLoS ONE 8(2), e57254 (2013).
136. Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am. J. Pathol. 158(1), 147-152 (2001).
137. Mahajan VB, Vallone JG, Lin JH et al. T-cell infiltration in autosomal dominant neovascular inflammatory vitreoretinopathy. Mol. Vis. 16, 1034-1040 (2010).
138. He C, Sun Y, Ren X et al. Angiogenesis mediated by toll-like receptor 4 in ischemic neural tissue. Arterioscler. Thromb. Vasc. Biol. 33(2), 330-338 (2013).
139. Tezel TH, Bodek E, Sönmez K et al. Targeting tissue factor for immunotherapy of choroidal neovascularization by intravitreal delivery of factor VII-Fc chimeric antibody. Ocul. Immunol. Inflamm. 15(1), 3-10 (2007).
140. Ferrara N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res. Treat. 36(2), 127-137 (1995).
141. Gao G, Li Y, Gee S et al. Down-regulation of vascular endothelial growth factor and up-regulation of pigment epitheliumderived factor: a possible mechanism for the anti-angiogenic activity of plasminogen kringle 5. J. Biol. Chem. 277(11), 9492-9497 (2002).
142. Lutty GA, Thompson DC, Gallup JY, Mello RJ, Patz A, Fenselau A. Vitreous: an inhibitor of retinal extract-induced neovascularization. Invest. Ophthalmol. Vis. Sci. 24(1), 52-56 (1983).
143. Lutty GA, Mello RJ, Chandler C, Fait C, Bennett A, Patz A. Regulation of cell growth by vitreous humour. J. Cell. Sci. 76, 53-65 (1985).
144. Gao G, Li Y, Fant J, Crosson CE, Becerra SP, Ma JX. Difference in ischemic regulation of vascular endothelial growth factor and pigment epithelium-derived factor in brown Norway and Sprague Dawley rats contributing to different susceptibilities to retinal neovascularization. Diabetes 51(4), 1218-1225 (2002).
145. Mohan N, Monickaraj F, Balasubramanyam M, Rema M, Mohan V. Imbalanced levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of patients with proliferative diabetic retinopathy. J. Diabetes Complicat. 26(5), 435-441 (2012).
146. Tombran-Tink J, Johnson LV. Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest. Ophthalmol. Vis. Sci. 30(8), 1700-1707 (1989).
147. Becerra SP, Sagasti A, Spinella P, Notario V. Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop. J. Biol. Chem. 270(43), 25992-25999 (1995).
148. Tombran-Tink J, Chader GG, Johnson LV. PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. Exp. Eye Res. 53(3), 411-414 (1991).
149. Steele FR, Chader GJ, Johnson LV, Tombran-Tink J. Pigment epitheliumderived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc. Natl Acad. Sci. USA 90(4), 1526-1530 (1993).
150. Becerra SP. Structure-function studies on PEDF. A noninhibitory serpin with neurotrophic activity. Adv. Exp. Med. Biol. 425, 223-237 (1997).
151. Araki T, Taniwaki T, Becerra SP, Chader GJ, Schwartz JP. Pigment epitheliumderived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death. J. Neurosci. Res. 53(1), 7-15 (1998).
152. Dawson DW, Volpert OV, Gillis P et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285(5425), 245-248 (1999).
153. Mori K, Duh E, Gehlbach P et al. Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J. Cell. Physiol. 188(2), 253-263 (2001).
154. Stellmach V, Crawford SE, Zhou W, Bouck N. Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epitheliumderived factor. Proc. Natl Acad. Sci. USA 98(5), 2593-2597 (2001).
155. Tombran-Tink J, Barnstable CJ. PEDF: a multifaceted neurotrophic factor. Nat. Rev. Neurosci. 4(8), 628-636 (2003).
156. Zhang SX, Ma JX, Sima J et al. Genetic difference in susceptibility to the bloodretina barrier breakdown in diabetes and oxygen-induced retinopathy. Am. J. Pathol. 166(1), 313-321 (2005).
157. Sheikpranbabu S, Haribalaganesh R, Lee KJ, Gurunathan S. Pigment epitheliumderived factor inhibits advanced glycation end products-induced retinal vascular permeability. Biochimie 92(8), 1040-1051 (2010).
158. Sheikpranbabu S, Ravinarayanan H, Elayappan B, Jongsun P, Gurunathan S. Pigment epithelium-derived factor inhibits vascular endothelial growth factor - and interleukin-1β-induced vascular permeability and angiogenesis in retinal endothelial cells. Vascul. Pharmacol. 52(1-2), 84-94 (2010).
159. Ogata N, Nishikawa M, Nishimura T, Mitsuma Y, Matsumura M. Unbalanced vitreous levels of pigment epitheliumderived factor and vascular endothelial growth factor in diabetic retinopathy. Am. J. Ophthalmol. 134(3), 348-353 (2002).
160. Boehm BO, Lang G, Volpert O et al. Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy. Diabetologia 46(3), 394-400 (2003).
161. Kim SY, Mocanu C, Mcleod DS et al. Expression of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in sickle cell retina and choroid. Exp. Eye Res. 77(4), 433-445 (2003).
162. Ogata N, Tombran-Tink J, Jo N, Mrazek D, Matsumura M. Upregulation of pigment epithelium-derived factor after laser photocoagulation. Am. J. Ophthalmol. 132(3), 427-429 (2001).
163. Spranger J, Osterhoff M, Reimann M et al. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes 50(12), 2641-2645 (2001).
164. Yang J, Williams RS, Kelly DP. Bcl3 interacts cooperatively with peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α to coactivate nuclear receptors estrogen-related receptor α and PPARα. Mol. Cell. Biol. 29(15), 4091-4102 (2009).
165. Shalom-Barak T, Nicholas JM, Wang Y et al. Peroxisome proliferator-activated receptor γ controls Muc1 transcription in trophoblasts. Mol. Cell. Biol. 24(24), 10661-10669 (2004).
166. Muranaka K, Yanagi Y, Tamaki Y et al. Effects of peroxisome proliferator-activated receptor γ and its ligand on blood-retinal barrier in a streptozotocin-induced diabetic model. Invest. Ophthalmol. Vis. Sci. 47(10), 4547-4552 (2006).
167. Lee KS, Kim SR, Park SJ et al. Peroxisome proliferator activated receptor-γ modulates reactive oxygen species generation and activation of nuclear factor-κB and hypoxia-inducible factor 1α in allergic airway disease of mice. J. Allergy Clin. Immunol. 118(1), 120-127 (2006).
168. Sung B, Park S, Yu BP, Chung HY. Amelioration of age-related inflammation and oxidative stress by PPARγ activator: suppression of NF-κB by 2,4-thiazolidinedione. Exp. Gerontol. 41(6), 590-599 (2006).
169. Song MK, Roufogalis BD, Huang TH. Modulation of diabetic retinopathy pathophysiology by natural medicines through PPAR-γ-related pharmacology. Br. J. Pharmacol. 165(1), 4-19 (2012).
170. Stahl A, Sapieha P, Connor KM et al. Short communication: PPAR γ mediates a direct antiangiogenic effect of ω 3-PUFAs in proliferative retinopathy. Circ. Res. 107(4), 495-500 (2010).
171. Murata T, He S, Hangai M et al. Peroxisome proliferator-activated receptor-γ ligands inhibit choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 41(8), 2309-2317 (2000).
172. Dougherty TJ, Marcus SL. Photodynamic therapy. Eur. J. Cancer 28A(10), 1734-1742 (1992).
173. Kaplan MJ, Somers RG, Greenberg RH, Ackler J. Photodynamic therapy in the management of metastatic cutaneous adenocarcinomas: case reports from Phase 1/2 studies using tin ethyl etiopurpurin (SnET2).J. Surg. Oncol. 67(2), 121-125 (1998).
174. Ben-Hur E, Orenstein A. The endothelium and red blood cells as potential targets in PDT-induced vascular stasis. Int. J. Radiat. Biol. 60(1-2), 293-301 (1991).
175. Flower RW. Optimizing treatment of choroidal neovascularization feeder vessels associated with age-related macular degeneration. Am. J. Ophthalmol. 134(2), 228-239 (2002).
176. Ho T, Smiddy WE, Flynn HW Jr. Vitrectomy in the management of diabetic eye disease. Surv. Ophthalmol. 37(3), 190-202 (1992).
177. Arrigg PG, Cavallerano J. The role of vitrectomy for diabetic retinopathy. J. Am. Optom. Assoc. 69(11), 733-740 (1998).
178. Sharma S, Brown GC, Brown MM, Hollands H, Shah GK. The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology 108(11), 2051-2059 (2001).
179. Shinoda K, Ishida S, Kawashima S et al. Clinical factors related to the aqueous levels of vascular endothelial growth factor and hepatocyte growth factor in proliferative diabetic retinopathy. Curr. Eye Res. 21(2), 655-661 (2000).
180. Drolet DW, Nelson J, Tucker CE et al. Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys. Pharm. Res. 17(12), 1503-1510 (2000).
181. Ruckman J, Green LS, Beeson J et al. 2′-fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165).
182. Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain. J. Biol. Chem. 273(32), 20556-20567 (1998).
183. Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N. Engl. J. Med. 351(27), 2805-2816 (2004).
184. Cunningham ET Jr, Adamis AP, Altaweel M et al.; Macugen Diabetic Retinopathy Study Group. A Phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 112(10), 1747-1757 (2005).
185. Nicholson BP, Schachat AP. A review of clinical trials of anti-VEGF agents for diabetic retinopathy. Graefes Arch. Clin. Exp. Ophthalmol. 248(7), 915-930 (2010).
186. Presta LG, Chen H, O'Connor SJ et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 57(20), 4593-4599 (1997).
187. Ellis LM, Curley SA, Grothey A. Surgical resection after downsizing of colorectal liver metastasis in the era of bevacizumab. J. Clin. Oncol. 23(22), 4853-4855 (2005).
188. Miller KD, Chap LI, Holmes FA et al. Randomized Phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J. Clin. Oncol. 23(4), 792-799 (2005).
189. Yang JC, Sherry RM, Steinberg SM et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J. Clin. Oncol. 21(16), 3127-3132 (2003).
190. Abouammoh M, Sharma S. Ranibizumab versus bevacizumab for the treatment of neovascular age-related macular degeneration. Curr. Opin. Ophthalmol. 22(3), 152-158 (2011).
191. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350(23), 2335-2342 (2004).
192. Arevalo JF, Fromow-Guerra J, Sanchez JG et al.; Pan-American Collaborative Retina Study Group. Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in age-related macular degeneration: results of the Pan-American Collaborative Retina Study Group at 12 months follow-up. Retina (Philadelphia, PA) 28(10), 1387-1394 (2008).
193. Willard AL, Herman IM. Vascular complications and diabetes: current therapies and future challenges. J. Ophthalmol. 2012, 209538 (2012).
194. Rosenfeld PJ, Brown DM, Heier JS et al.; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355(14), 1419-1431 (2006).
195. Nguyen QD, Shah SM, Khwaja AA et al.; READ-2 Study Group. Two-year outcomes of the ranibizumab for edema of the macula in diabetes (READ-2) study. Ophthalmology 117(11), 2146-2151 (2010).
196. Holash J, Davis S, Papadopoulos N et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc. Natl Acad. Sci. USA 99(17), 11393-11398 (2002).
197. Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V. Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration. Invest. Ophthalmol. Vis. Sci. 46(2), 726-733 (2005).
198. Rakic JM, Zelinkova M, ComhairePoutchinian Y, Galand A, Duchateau E. Treatment of Graves macular edema with intravitreal injection of corticosteroids. Bull. Soc. Belge Ophtalmol. 288, 43-48 (2003).
199. Brown DM, Kaiser PK, Michels M et al.; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N. Engl. J. Med. 355(14), 1432-1444 (2006).
200. Kaiser PK; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical trials with an open-label extension: TAP report no. 8. Graefes Arch. Clin. Exp. Ophthalmol. 244(9), 1132-1142 (2006).
201. Kaiser PK. Antivascular endothelial growth factor agents and their development: therapeutic implications in ocular diseases. Am. J. Ophthalmol. 142(4), 660-668 (2006).
202. Essex RW, Tufail A, Bunce C, Aylward GW. Two-year results of surgical removal of choroidal neovascular membranes related to non-age-related macular degeneration. Br. J. Ophthalmol. 91(5), 649-654 (2007).
203. Xu H, Chen M, Forrester JV. Para- inflammation in the aging retina. Prog. Retin. Eye Res. 28(5), 348-368 (2009).
204. Leal EC, Santiago AR, Ambrósio AF. Old and new drug targets in diabetic retinopathy: from biochemical changes to inflammation and neurodegeneration. Curr. Drug Targets CNS Neurol. Disord. 4(4), 421-434 (2005).
205. Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH. Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to Drusen formation and age-related macular degeneration. PLoS ONE 4(1), e4160 (2009).
206. Simó R, Hernández C. Intravitreous anti-VEGF for diabetic retinopathy: hopes and fears for a new therapeutic strategy. Diabetologia 51(9), 1574-1580 (2008).
207. Wirostko B, Wong TY, Simó R. Vascular endothelial growth factor and diabetic complications. Prog. Retin. Eye Res. 27(6), 608-621 (2008).
208. Day S, Acquah K, Mruthyunjaya P, Grossman DS, Lee PP, Sloan FA. Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration. Am. J. Ophthalmol. 152(2), 266-272 (2011).
209. Wulff C, Wilson H, Wiegand SJ, Rudge JS, Fraser HM. Prevention of thecal angiogenesis, antral follicular growth, and ovulation in the primate by treatment with vascular endothelial growth factor Trap R1R2. Endocrinology 143(7), 2797-2807 (2002).
210. Ni Z, Hui P. Emerging pharmacologic therapies for wet age-related macular degeneration. Ophthalmologica 223(6), 401-410 (2009).
211. Danis RP, Bingaman DP, Jirousek M, Yang Y. Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKCβ inhibition with LY333531. Invest. Ophthalmol. Vis. Sci. 39(1), 171-179 (1998).
212. Bursell SE, Clermont AC, Kinsley BT, Simonson DC, Aiello LM, Wolpert HA. Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 37(5), 886-897 (1996).
213. Aiello LP, Bursell SE, Clermont A et al. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective β-isoform-selective inhibitor. Diabetes 46(9), 1473-1480 (1997).
214. Feke GT, Buzney SM, Ogasawara H et al. Retinal circulatory abnormalities in Type 1 diabetes. Invest. Ophthalmol. Vis. Sci. 35(7), 2968-2975 (1994).
215. Xu X, Zhu Q, Xia X, Zhang S, Gu Q, Luo D. Blood-retinal barrier breakdown induced by activation of protein kinase C via vascular endothelial growth factor in streptozotocin-induced diabetic rats. Curr. Eye Res. 28(4), 251-256 (2004).
216. Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA. Inhibition of protein kinase Cβ prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ. Res. 90(1), 107-111 (2002).
217. Strøm C, Sander B, Klemp K, Aiello LP, Lund-Andersen H, Larsen M. Effect of ruboxistaurin on blood-retinal barrier permeability in relation to severity of leakage in diabetic macular edema. Invest. Ophthalmol. Vis. Sci. 46(10), 3855-3858 (2005).
218. Schwartz SG, Flynn HW Jr, Aiello LP. Ruboxistaurin mesylate hydrate for diabetic retinopathy. Drugs Today 45(4), 269-274 (2009).
219. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669), 806-811 (1998).
220. Kaiser PK, Symons RC, Shah SM et al.; siRNA-027 Study Investigators. RNAibased treatment for neovascular age-related macular degeneration by siRNA-027. Am. J. Ophthalmol. 150(1), 33.e2-39.e2 (2010).
221. Shen J, Samul R, Silva RL et al. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Ther. 13(3), 225-234 (2006).
222. Ceda GP, Hoffman AR, Silverberg GD, Wilson DM, Rosenfeld RG. Regulation of growth hormone release from cultured human pituitary adenomas by somatomedins and insulin. J. Clin. Endocrinol. Metab. 60(6), 1204-1209 (1985).
223. Smith LE, Kopchick JJ, Chen W et al. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 276(5319), 1706-1709 (1997).
224. Gilbert RE, Kelly DJ, Cox AJ et al. Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes. Diabetologia 43(11), 1360-1367 (2000).
225. Williams B, Baker AQ, Gallacher B, Lodwick D. Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. Hypertension 25(5), 913-917 (1995).
226. Chua CC, Hamdy RC, Chua BH. Upregulation of vascular endothelial growth factor by angiotensin II in rat heart endothelial cells. Biochim. Biophys. Acta 1401(2), 187-194 (1998).
227. Goa KL, Haria M, Wilde MI. Lisinopril. A review of its pharmacology and use in the management of the complications of diabetes mellitus. Drugs 53(6), 1081-1105 (1997).
228. Scatena R. Prinomastat, a hydroxamatebased matrix metalloproteinase inhibitor. A novel pharmacological approach for tissue remodelling-related diseases. Expert Opin. Investig. Drugs 9(9), 2159-2165 (2000).
229. Shalinsky DR, Brekken J, Zou H et al. Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann. N. Y. Acad. Sci. 878, 236-270 (1999).
230. Garcia C, Bartsch DU, Rivero ME et al. Efficacy of prinomastat (AG3340), a matrix metalloprotease inhibitor, in treatment of retinal neovascularization. Curr. Eye Res. 24(1), 33-38 (2002).
231. Spandau UH, Sauder G, Schubert U, Hammes HP, Jonas JB. Effect of triamcinolone acetonide on proliferation of retinal endothelial cells in vitro and in vivo. Br. J. Ophthalmol. 89(6), 745-747 (2005).
232. Wang YS, Friedrichs U, Eichler W, Hoffmann S, Wiedemann P. Inhibitory effects of triamcinolone acetonide on bFGF-induced migration and tube formation in choroidal microvascular endothelial cells. Graefes Arch. Clin. Exp. Ophthalmol. 240(1), 42-48 (2002).
233. Koedam JA, Smink JJ, van Buul-Offers SC. Glucocorticoids inhibit vascular endothelial growth factor expression in growth plate chondrocytes. Mol. Cell. Endocrinol. 197(1-2), 35-44 (2002).
234. Gille J, Reisinger K, Westphal-Varghese B, Kaufmann R. Decreased mRNA stability as a mechanism of glucocorticoid-mediated inhibition of vascular endothelial growth factor gene expression by cultured keratinocytes. J. Invest. Dermatol. 117(6), 1581-1587 (2001).
235. Nauck M, Karakiulakis G, Perruchoud AP, Papakonstantinou E, Roth M. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur. J. Pharmacol. 341(2-3), 309-315 (1998).
236. Jamrozy-Witkowska A, Kowalska K, Jankowska-Lech I, Terelak-Borys B, Nowosielska A, Grabska-Liberek I. Complications of intravitreal injections - own experience. Klin. Oczna 113(4-6), 127-131 (2011).
237. Shah AM, Oster SF, Freeman WR. Viral retinitis after intravitreal triamcinolone injection in patients with predisposing medical comorbidities. Am. J. Ophthalmol. 149(3), 433.e1-440.e1 (2010).
238. Wilkinson-Berka JL, Alousis NS, Kelly DJ, Gilbert RE. COX-2 inhibition and retinal angiogenesis in a mouse model of retinopa- thy of prematurity. Invest. Ophthalmol. Vis. Sci. 44(3), 974-979 (2003).
239. Carmo A, Cunha-Vaz JG, Carvalho AP, Lopes MC. Nitric oxide synthase activity in retinas from non-insulin-dependent diabetic Goto-Kakizaki rats: correlation with blood-retinal barrier permeability. Nitric Oxide 4(6), 590-596 (2000).
240. Takahashi K, Saishin Y, Saishin Y et al. Topical nepafenac inhibits ocular neovascularization. Invest. Ophthalmol. Vis. Sci. 44(1), 409-415 (2003).
241. Zheng Z, Schwab S, Grau A, Berger C. Neuroprotection by early and delayed treatment of acute stroke with high dose aspirin. Brain Res. 1186, 275-280 (2007).
242. Yrjänheikki J, Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc. Natl Acad. Sci. USA 96(23), 13496-13500 (1999).
243. Elewa HF, Hilali H, Hess DC, Machado LS, Fagan SC. Minocycline for short-term neuroprotection. Pharmacotherapy 26(4), 515-521 (2006).
244. Baptiste DC, Hartwick AT, Jollimore CA, Baldridge WH, Seigel GM, Kelly ME. An investigation of the neuroprotective effects of tetracycline derivatives in experimental models of retinal cell death. Mol. Pharmacol. 66(5), 1113-1122 (2004).
245. Roychoudhury J, Herndon JM, Yin J, Apte RS, Ferguson TA. Targeting immune privilege to prevent pathogenic neovascularization. Invest. Ophthalmol. Vis. Sci. 51(7), 3560-3566 (2010).
246. Funatsu H, Yamashita H, Noma H et al. Outcome of vitreous surgery and the balance between vascular endothelial growth factor and endostatin. Invest. Ophthalmol. Vis. Sci. 44(3), 1042-1047 (2003).
247. Lai CC, Wu WC, Chen SL et al. Recombinant adeno-associated virus vector expressing angiostatin inhibits preretinal neovascularization in adult rats. Ophthalmic Res. 37(1), 50-56 (2005).