158
Views
31
CrossRef citations to date
0
Altmetric
Review

Strategies for blocking angiogenesis in diabetic retinopathy: from basic science to clinical practice

&
Pages 1209-1226 | Published online: 09 Aug 2007

Bibliography

  • MOSS SE, KLEIN R, KLEIN BE: The 14-year incidence of visual loss in a diabetic population. Ophthalmology (1998) 105(6):998-1003.
  • TONG L, VERNON SA, KIEL W, SUNG V, ORR GM: Association of macular involvement with proliferative retinopathy in Type 2 diabetes. Diabet. Med. (2001) 18(5):388-394.
  • KLEIN R, KLEIN BE, MOSS SE, DAVIS MD, DEMETS DL: The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch. Ophthalmol. (1984) 102(4):527-532.
  • DIABETES COMPLICATIONS AND CONTROL TRIAL STUDY GROUP: The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. Arch. Ophthalmol. (1995) 113(1):36-51.
  • UK PROSPECTIVE DIABETES STUDY (UKDPS) GROUP: Intensive blood–glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes (UKDPS 33). Lancet (1998) 352(9131):837-853.
  • UK PROSPECTIVE DIABETES STUDY (UKDPS) GROUP: Tight blood pressure control and risk of macrovascular and microvascular complications in Type 2 diabetes: UKPDS 28. Br. Med. J. (1998) 317(7160):703-713.
  • FINE SL, PATZ A: Ten years after Diabetic Retinopathy Study. Ophthalmology (1987) 94(7):739-740.
  • BARRY P: The management of diabetic eye disease. In: Textbook of Diabetes. Pickup JC, Williams G (Eds), Blackwell Science, Oxford, UK (1997):47.41-47.42.
  • SIMO R, CARRASCO M, GARCIA-RAMIREZ M, HERNÁNDEZ C: Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr. Diabet. Rev. (2006) 2:71-98.
  • SIMO R: Angiogenic and antiangiogenic factors in diabetic retinopathy. Endocrinología y Nutrición (2006) 53(4):233-236.
  • GIARDINO I, BROWNLEE M: The biochemical basis of microvascular disease. In: Textbook of Diabetes. Pickup JC, Williams G (Eds), Blackwell Science, Oxford, UK (1997):42.1-42.16.
  • BROWNLEE M: Biochemistry and molecular cell biology of diabetic complications. Nature (2001) 414(6865):813-820.
  • ZHANG J, GERHARDINGER C, LORENZI M: Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitor in human and experimental diabetic retinopathy. Diabetes (2002) 51(12):3499-3504.
  • JOUSSEN AM, POULAKI V, LE ML et al.: A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. (2004) 18(12):1450-1452.
  • 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 (2003) 110(9):1690-1696.
  • NGUYEN QD, TATLIPINAR S, SHAH SM et al.: Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am. J. Ophthalmol. (2006) 142(6):961-969.
  • ARJAMAA O, NIKINMAA M: Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. Exp. Eye Res. (2006) 83(3):473-483.
  • HANAHAN D, FOLKMAN J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell (1996) 86(3):353-364.
  • SMITH L, WESOLOWSKI E, MCLELLAN A, KOSTYK S, D'AMATO R, SULLIVAN R: Oxygen-induced retinopathy in the mouse. Invest. Ophthalmol. Vis. Sci. (1994) 35(1):101-111.
  • AIELLO L, PIERCE E, FOLEY E 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 (1995) 92(23):10457-10461.
  • ADAMIS A, SHIMA D, TOLENTINO M et al.: Inhibition of VEGF prevents ocular neovascularization in a non-human primate. Arch. Ophthalmol. (1996) 114(1):66-71.
  • SUZUMA K, TAKAGI H, OTANI A, SUZUMA I, HONDA Y: Increased expression of KDR/Flk-1 (VEGFR-2) in murine model of ischemia-induced retinal neovascularization. Microvas. Res. (1998) 56(3):183-191.
  • HAMMES H, LIN J, BRETZEL R, BROWNLEE M, BREIER G: Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. Diabetes (1998) 47(3):401-406.
  • ELLIS EA, GUBERSKI DL, SOMOGYI-MANN M, GRANT MB: Increased H2O2, vascular endothelial growth factor and receptors in the retina of the BBZ/W or diabetic rat. Free Radic. Biol. Med. (2000) 28(1):91-101.
  • QAUM T, XU Q, JOUSSEN AM et al.: VEGF-initiated blood–retinal barrier breakdown in early diabetes. Invest. Ophthalmol. Vis. Sci. (2001) 42(10):2408-2413.
  • AMIN RH, FRANK RN, KENNEDY A, ELIOTT D, PUKLIN JE, ABRAMS GW: Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. (1997) 38(1):36-47.
  • BOULTON M, FOREMAN D, WILLIAMS G, MCLEOD D: VEGF localisation in diabetic retinopathy. Br. J. Ophthalmol. (1998) 82(5):561-568.
  • SPRANGER J, OSTERHOFF M, REIMANN M et al.: Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes (2001) 50(12):2641-2645.
  • OGATA N, TOMBRAN-TINK J, NISHIKAWA M et al.: Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy and high in rhegmatogenous retinal detachment. Am. J. Ophthalmol. (2001) 132(3):378-382.
  • MORI K, GEHLBACH P, ANDO A, MCVEY D, WEI L, CAMPOCHIARO PA: Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor. Invest. Ophthalmol. Vis. Sci. (2002) 43(7):2428-2434.
  • ZHANG SX, WANG JJ, GAO G, PARKE K, MA JX: 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.
  • LIU H, REN JG, COOPER WL, HAWKINS CE, COWAN MR, TONG PY: Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site. Proc. Natl. Acad. Sci. USA (2004) 27(17):6605-6610.
  • YAMAGISHI S, INAGAKI Y, AMANO S, OKAMOTO T, TAKEUCHI M, MAKITA Z: Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its antioxidative properties. Biochem. Biophys. Res. Commun. (2002) 296(4):877-882.
  • FELTON SM, BROWN GC, FELBERG NT, FEDERMAN JL: Vitreous inhibition of tumor neovascularization. Arch. Ophthalmol. (1979) 97(9):1710-1713.
  • LUTTY GA, MELLO RJ, CHANDLER C, FAIT C, BENNETT A, PATZ A: Regulation of cell growth by vitreous humour. J. Cell Sci. (1985) 76(1):53-65.
  • WEGEWITZ U, GöRING I, SPRANGER J: Novel approaches in the treatment of angiogenic eye disease. Curr. Pharm. Design (2005) 11(18):2311-2330.
  • BAINBRIDGE JW, MISTRY A, TRASHER AJ, ALI RR: Gene theraphy for ocular angiogenesis. Clin. Sci. (2003) 104(6):561-575.
  • BORRAS T: Recent developments in ocular gene therapy. Exp. Eye Res. (2003) 76(6):643-652.
  • REICH SJ, BENNETT J: Gene therapy for ocular neovascularization: a cure in sight. Curr. Opin. Genet. Dev. (2003) 13(3):317-322.
  • KOYA D, KING GL: Protein kinase C activation and the development of diabetic complications. Diabetes (1998) 47(6):859-866.
  • XIA P, INOGOUCHI T, KERN TS, ENGERMAN RL, OATES PJ, KING GL: Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes (1994) 43(9):1122-1129.
  • PORTILLA D, DAI G, PETERS JM, GONZALEZ FJ, CREW MD, PROIA AD: Etomoxir-induced PPARα-modulated enzymes protect during acute renal failure. Am. J. Physiol. Renal Physiol. (2000) 278(4):F667-F675.
  • KEOGH RJ, DUNLOP ME, LARKINS RG: Effect of inhibition of aldose reductase on glucose flux, diacylglycerol formation, protein kinase C, and phospholipase A2 activation. Metabolism (1997) 46(1):41-47.
  • TOMLINSON DR: Mitogen-activated protein kinases as glucose transducers for diabetic complications. Diabetologia (1999) 42(11):1271-1281.
  • KOWLURU RA: Diabetes-induced elevations in retinal oxidative stress, protein kinase C and nitric oxide are interrelated. Acta Diabetol. (2001) 38(4):179-185.
  • INOGOUCHI T, BATTAN R, HANDLER E, SPORTSMAN JR, HEATH W, KING GL: Preferential elevation of protein kinase C isoform β II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc. Natl. Acad. Sci. USA (1992) 89(22):11059-11063.
  • XIA P, AIELLO LP, ISHII H et al.: Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J. Clin. Invest. (1996) 98(9):2018-2026.
  • 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 (1997) 46(9):1473-1780.
  • SUZUMA K, TAKAHARA N, SUZUMA I et al.: Characterization of protein kinase C β isoform's action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization. Proc. Natl. Acad. Sci. USA (2002) 99(2):721-726.
  • YOUNG TA, WANG H, MUNK S et al.: Vascular endothelial growth factor expression and secretion by retinal pigment epithelial cells in high glucose and hypoxia is protein kinase C-dependent. Exp. Eye Res. (2005) 80(5):651-662.
  • POULAKI V, QIN W, JOUSSEN AM et al.: Acute intensive insulin therapy exacerbates diabetic blood–retinal barrier breakdown via hypoxia-inducible factor-1α and VEGF. J. Clin. Invest. (2002) 109(6):805-815.
  • 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 Dis. (2004) 28(4):251-256.
  • OHSHIRO Y, MA RC, YASUDA Y et al.: Reduction of diabetes-induced oxidative stress, fibrotic cytokine expression, and renal dysfunction in protein kinase C β-null mice. Diabetes (2006) 55(11):3112-3120.
  • FABBRO D, RUETZ S, BODIS S et al.: PKC412 – a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. (2000) 15(1):17-28.
  • SEO MS, KWAK N, OZAKI H et al.: Dramatic inhibition of retinal and choroidal neovascularization by oral administration of a kinase inhibitor. Am. J. Pathol. (1999) 154(6):1743-1753.
  • PROPPER DJ, McDONALD AC, MAN A et al.: Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J. Clin. Oncol. (2001) 19(5):1485-1492.
  • CAMPOCHIARO PA; C99-PKC412-003 STUDY GROUP: Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412. Invest. Ophthalmol. Vis. Sci. (2004) 45(3):922-931.
  • SAISHIN Y, SILVA RL, SAISHIN Y et al.: Periocular injection of microspheres containing PKC412 inhibits choroidal neovascularization in a porcine model. Invest. Ophthalmol. Vis.Sci. (2003) 44(4):4989-4993.
  • BURSELL SE, TAKAGI C, CLERMONT AC et al.: Specific retinal diacylglycerol and protein kinase C β isoform modulation mimics abnormal retinal hemodynamics in diabetic rats. Invest. Ophthalmol. Vis. Sci. (1997) 38(13):2711-2720.
  • KOWLURU RA, JIROUSEK MR, STRAMM L, FARID N, ENGERMAN RL, KERN TS: Abnormalities of retinal metabolism in diabetes or experimental galactosemia: V. Relationship between protein kinase C and ATPases. Diabetes (1998) 47(3):464-469.
  • COTTER MA, JACK AM, CAMERON NE: Effects of the protein kinase C β inhibitor LY333531 on neural and vascular function in rats with streptozotocin-induced diabetes. Clin. Sci. (Lond.) (2002) 103(3):311-321.
  • NONAKA A, KIRYU J, TSUJIKAWA A et al.: PKC-β inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest. Ophthalmol. Vis. Sci. (2000) 41(9):2702-2706.
  • AIELLO JP, CLERMONT A, ARORA V, DAVIS MD, SHEETZ MJ, BURSELL SE: Inhibition of PKC β by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients. Invest. Ophthalmol. Vis. Sci. (2006) 47(1):86-92.
  • 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. (1998) 39(1):171-179.
  • DEMOLLE D, DE SURAY JM, ONKELINX C: Pharmacokinetics and safety of multiple oral dose of LY333531, a PKCβ inhibitor, in healthy subjects. Clin. Pharmacol. Ther. (1999) 39(1):171-179.
  • THE PKC-DRS STUDY GROUP: The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C β Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. Diabetes (2005) 54(7):2188-2197.
  • PKC-DRS2 GROUP; AIELLO LP, DAVIS MD, GIRACH A et al.: Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology (2006) 113(12):2221-2230.
  • POULSEN JE: Recovery from retinopathy in a case of diabetes with Simmonds' disease. Diabetes (1953) 2(1):7-12.
  • GRANT MB, MAMES RN, FITZGERALD C et al.: The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomised controlled study. Diabetes Care (2000) 23(4):504-509.
  • BOEHM BO, LANG GK, JEHLE PM, FELDMAN B, LANG GE: Octreotide reduces vitreous hemorrhage and loss of visual acuity risk in patients with high-risk proliferative diabetic retinopathy. Horm. Metab. Res. (2001) 33(5):300-306.
  • JANSSEN J, LAMBERTS S: Circulating IGF-1 and its protective role in the pathogenesis of diabetic angiopathy. Clin. Endocrinol. (2000) 52(1):1-9.
  • LAMBOOIJ AC, KUIJPERS RW, VAN LICHTENAUER-KALIGIS EG et al.: Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. (2000) 41(8):2329-2335.
  • KLISOVIC DD, O'DORISIO MS, KATZ SE et al.: Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study. Invest. Ophthalmol. Vis. Sci. (2001) 42(10):2193-2201.
  • WILSON SH, DAVIS MI, CABALLERO S, GRANT MB: 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.
  • GRANT MB, CABALLERO S, MILLARD WJ: Inhibition of IGF-1 and b-FGF stimulated growth of human retinal endothelial cells by the somatostatin analogue, octreotide: a potential treatment for ocular neovascularization. Reg. Peptides (1993) 48(1-2):267-278.
  • DAVIS MI, WILSON SH, GRANT MB: The therapeutic problem of proliferative diabetic retinopathy: targeting somatostatin receptors. Horm. Metab. Res. (2001) 33(5):295-299.
  • SALL JW, KLISOVIC DD, O'DORISIO MS, KATZ SE: Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cells. Exp. Eye Res. (2004) 79(4):465-476.
  • BALDYSIAK-FIGIEL A, LANG GK, KAMPMEIER J, LANG GE: Octreotide prevents growth factor-induced proliferation of bovine retinal endothelial cells under hypoxia. J. Endocrinol. (2004) 180(3):417-424.
  • SIMO R, LECUBE A, SARAROLS L, GARCIA-ARUMI J, SEGURA RM, HERNANDEZ C: Deficit of somatostatin-like immunoreactivity in the vitreous fluid of diabetic patients. Diabetes Care (2002) 25(12):2282-2286.
  • SIMO R, CARRASCO E, FONOLLOSA A, GARCIA-ARUMI J, CASAMITJANA R, HERNANDEZ C: Deficit of somatostatin in the vitreous fluid of patients with diabetic macular edema. Diabetes Care (2007) 30(3):725-727.
  • HERNANDEZ C, CARRASCO E, CASAMITJANA R, DEULOFEU R, GARCIA-ARUMI J, SIMO R: Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and non-diabetic control subjects. Diabetes Care (2005) 28(8):1941-1947.
  • CARRASCO E, HERNANDEZ C, MIRALLES A, MESA J, FARRES J, SIMO R: Deficit of somatostatin expression in diabetic human retina: and early event in the pathogenesis of diabetic retinopathy. Diabetologia (2006) 49(Suppl. 1):158-159.
  • YASUKAWA T, OGURA Y, TABATA Y, KIMURA H, WIEDEMANN P, HONDA Y: Drug delivery systems for vitreoretinal diseases. Prog. Retin. Eye Res. (2004) 23(3):253-281.
  • MAURICE D: Characterization of paracellular penetration routes. Invest. Ophthalmol. Vis. Sci. (1997) 38(11):2177-2180.
  • GEROSKI DH, EDELHAUSER HF: Drug delivery for posterior segment eye disease. Invest. Ophthalmol. Vis. Sci. (2000) 41(5):961-964.
  • MYLES ME, NEUMANN DM, HILL J: Recent progress in ocular drug delivery for posterior segment disease: emphasis on transscleral iontophoresis. Adv. Drug Deliv. Rev. (2005) 57(14):2063-2079.
  • JACKSON TL, ANTCLIFF RJ, HILLENKAMP J, MARSHALL J: Human retinal molecular weight exclusion limit and estimate of species variation. Invest. Ophthalmol. Vis. Sci. (2003) 44(5):2141-2146.
  • KURZ D, CIULLA TA: Novel approaches for retinal drug delivery. Ophthalmol. Clin. North Am. (2002) 15(3):405-410.
  • MAURICE D: Practical issues in intravitreal drug delivery. J. Ocul. Pharmacol. Ther. (2001) 17(4):393-340.
  • NG EW, SHIMA DT, CALIAS P, CUNNINGHAM ET Jr, GUYER DR, ADAMIS AP: Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat. Rev. Drug Discov. (2006) 5(2):123-132.
  • VAN WIJNGAARDEN P, COSTER DJ, WILLIAMS KA: Inhibitors of ocular neovascularization: promises and potential problems. JAMA (2005) 293(12):1509-1513.
  • EYETECH STUDY GROUP: Preclinical and Phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina (2002) 22(2):143-152.
  • ISHIDA S, USUI T, YAMASHIRO K et al.: VEGF164(165) as the pathological isoform: differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. Invest. Ophthalmol. Vis. Sci. (2004) 45(2):368-374.
  • GRAGOUDAS ES, ADAMIS AP, CUNNINGHAM ET Jr, FEINSOD M, GUYER DR: Pegaptanib for neovascular age-related macular degeneration. N. Engl. J. Med. (2004) 351(27):2805-2816.
  • D'AMICO DJ; VEGF Inhibition Study IN Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group; PATEL M, ADAMIS AP, CUNNINGHAM ET Jr, GUYER DR, KATZ B: Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology (2006) 113(6):1001.e1-1001.e6.
  • VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group; CHAKRAVARTHY U, ADAMIS AP, CUNNINGHAM ET Jr et al.: Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration. Ophthalmology (2006) 113(9):1508.e1-1508.e25.
  • CUNNINGHAN ET Jr, ADAMIS AP, ALTAWEEL M et al.: A Phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology (2005) 112(10):1747-1757.
  • ADAMIS AP, ALTAWEEL M, BRESSLER NM et al.: Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology (2006) 113(1):23-28.
  • KIM KJ, LI B, HOUCK K et al.: The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors (1992) 7(1):53-64.
  • CHEN Y, WIESMANN C, FUH G et al.: Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. J. Mol. Biol. (1999) 293(4):865-881.
  • 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. (1997) 57(20):4593-4599.
  • MORDENTI J, CUTHBERTSON RA, FERRARA N et al.: Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol. Pathol. (1999) 27(5):536-544.
  • KRZYSTOLIK MG, AFSHARI MA, ADAMIS AP et al.: Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch. Ophthalmol. (2002) 120(3):338-346.
  • HEIER JS, SY JS, McCLUSKEY ER: RhuFab V2 in wet AMD-6 month improvement following multiple intravitreal injections. Invest. Ophthalmol. Vis. Sci. (2003) 44:e-abstract 972.
  • ROSENFELD PJ, BROWN DM, HEIER JS et al.: Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. (2006) 355(14):1419-1431.
  • BROWN DM, KAISER PK, MICHELS M et al.: Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N. Engl. J. Med. (2006) 355(14):1432-1444.
  • CHUN DW, HEIER JS, TOPPING TM, DUKER JS, BANKERT JM: A pilot study of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema. Ophthalmology (2006) 113(10):1706-1712.
  • KAISER PK: Antivascular endothelial growth factor agents and their development: therapeutic implications in ocular diseases. Am. J. Ophthalmol. (2006) 142(4):660-668.
  • ROSENFELD PJ, MOSHFEGHI AA, PULIAFITO CA: Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg. Lasers Imaging (2005) 36(4):331-335.
  • LAZIC R, GABRIC N: Intravitreally administered bevacizumab (Avastin) in minimally classic and occult choroidal neovascularization secondary to age-related macular degeneration. Graefes. Arch. Clin. Exp. Ophthalmol. (2007) 245(1):68-73.
  • ROSENFELD PJ, FUNG AE, PULIAFITO CA: Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg. Lasers Imaging (2005) 36(4):336-339.
  • ITURRALDE D, SAPIDE RF, MEYERLE CB et al.: Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal vein occlusion: a short-term study. Retina (2006) 26(3):279-284.
  • FEINER L, BARR EE, SHUI YB, HOLEKAMP NM, BRANTLEY MA Jr: Safety of intravitreal injection of bevacizumab in rabbit eyes. Retina (2006) 26(8):882-888.
  • MANZANO RP, PEYMAN GA, KHAN P, KIVILCIM M: Testing intravitreal toxicity of bevacizumab (Avastin). Retina (2006) 26(3):257-261.
  • MASON JO III, NIXON PA, WHITE MF: Intravitreal injection of bevacizumab (Avastin) as adjunctive treatment of proliferative diabetic retinopathy. Am. J. Ophthalmol. (2006) 142(4):685-688.
  • AVERY RL, PEARLMAN J, PIERAMICI DJ et al.: Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology (2006) 113(10):1695.e1-1695.e15.
  • STEINBROOK R: The price of sight – ranibizumab, bevacizumab, and the treatment of macular degeneration. N. Engl. J. Med. (2006) 355(14):1409-1412.
  • YOSHIDA A, YOSHIDA S, KHALIL AK, ISHIBASHI T, INOMATA H: Role of NF-κB-mediated interleukin-8 expression in intraocular neovascularization. Invest. Ophthalmol. Vis. Sci. (1998) 39(7):1097-1106.
  • JOUSSEN AM, POULAKI V, MITSIADES N et al.: Nonesteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-α suppression. FASEB J. (2002) 16(3):438-440.
  • JOUSSEN AM, POULAKI V, QIN W et al.: Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo. Am. J. Pathol. (2002) 160(2):501-509.
  • HERNANDEZ C, SEGURA RM, FONOLLOSA A, CARRASCO E, FRANCISCO G, SIMO R: Interleukin-8, monocyte chemotactic protein-1 and interleukin-10 in the vitreous fluid of patients with proliferative diabetic retinopathy. Diabet. Med. (2005) 22(6):719-722.
  • BANDELLO F, POGNUZ R, POLITO A, PIRRACCHIO A, MENCHINI F, AMBESI M: Diabetic macular edema: classification, medical and laser therapy. Semin. Ophthalmol. (2003) 18(4):251-258.
  • MASSIN P, AUDREN F, HAOUCHINE B et al.: Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology (2004) 111(2):218-224.
  • JONAS JB, AKKOYUN I, KREISSIG I, DEGENRING RF: Diffuse diabetic macular oedema treated by intravitreal triamcinolone acetonide: a comparative, non-randomised study. Br. J. Ophthalmol. (2005) 89(3):321-326.
  • 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. (1998) 341(2-3):309-315.
  • NAUCK M, ROTH M, TAMM M et al.: Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids. Am. J. Respir. Cell. Mol. Biol. (1997) 16(4):398-406.
  • PENN JS, RAJARATNAM VA, COLLIER RJ, CLARK AF: The effect of an angiostatic steroid on neovascularization in a rat model of retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. (2001) 42(1):283-290.
  • SLAKTER JS, BOCHOW TW, D'AMICO DJ et al.: Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration. Ophthalmology (2006) 113(1):3-13.
  • MINER JN, HONG MH, NEGRO-VILAR A: New and improved glucocorticoid receptor ligands. Expert Opin. Investig. Drugs (2005) 14(12):1527-1545.
  • CASTRO MR, LUTZ D, EDELMAN JL: Effect of COX inhibitors on VEGF-induced retinal vascular leakage and experimental corneal and choroidal neovascularization. Exp. Eye Res. (2004) 79(2):275-285.
  • KRADY JK, BASU A, ALLEN CM et al.: Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes (2005) 54(5):1559-1565.
  • VINCENT JA, MOHR S: Inhibition of caspase-1/interleukin-1β signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes (2007) 56(1):224-230.
  • ANAND V, DUFFY B, YANG Z, DEJNEKA NS, MAGUIRE AM, BENNETT J: A deviant immune response to viral proteins and transgene product is generated generated on subretinal administration of adenovirus and adeno-associated virus. Mol. Ther. (2002) 5(2):125-132.
  • SURACE M, AURICCHIO A: Adeno-associated viral vectors for retinal gene transfer. Prog. Retin. Eye Res. (2003) 22(6):705-719.
  • DEJNEKA NS, AURICCHIO A, MAGUIRE AM et al.: Pharmacologically regulated gene expression in the retina following transduction with viral vectors. Gene. Ther. (2001) 8(6):442-446.
  • AURICCHIO A, RIVERA VM, CLACKSON T et al.: Pharmacological regulation of protein expression from adeno-associated viral vectors in the eye. Mol. Ther. (2002) 6(2):238-242.
  • CAMPOCHIARO PA, NGUYEN QD, SHAH SM et al.: Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a Phase I clinical trial. Hum. Gene Ther. (2006) 17(2):167-176.
  • RAYMOND PA, HITCHCOCK PF: Retinal regeneration: common principles but a diversity of mechanisms. Adv. Neurol. (1997) 72:171-184.
  • GOTO T, HISATOMI O, KOTOURA M, TOKUNAGA F: Induced expression of hematopoietic- and neurologic-expressed sequence 1 in retinal pigment epithelial cells during newt retina regeneration. Exp. Eye Res. (2006) 83(4):972-980.
  • KLANSEN H, ZIAEIAN B, KIROV II et al.: Isolation of retinal progenitor cells from post-mortem human tissue and comparison with autologous brain progenitors. J. Neurosci. Res. (2004) 77(3):334-343.
  • COLES BL, ANGENIEUX B, INOUE T et al.: Facile isolation and characterization of human retinal stem cells. Proc. Natl. Acad. Sci. USA (2004) 101(44):15772-15777.
  • MAYER EJ, CARTER DA, REN Y et al.: Neural progenitor cells from postmortem adult retina. Br. J. Ophthal. (2005) 89(1):102-106.
  • GRANT MB, MAY WS, CABALLERO S et al.: Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat. Med. (2002) 8(6):607-612.
  • OTANI A, KINDER K, EWALT K, OTERO FJ, SCHIMMEL P, FRIEDLANDER M: Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat. Med. (2002) 8(9):1004-1010.
  • CHAN-LING T, BAXTER L, AFZAL A et al.: Hematopoietic stem cells provide repair functions after laser-induced Bruch's membrane rupture model of choroidal neovascularization. Am. J. Pathol. (2006) 168(3):1031-1044.
  • MACLAREN RE, PEARSON RA, MACNEIL A et al.: Retinal repair by transplantation of photoreceptor precursors. Nature (2006) 444(7116):203-207.
  • LI Y, RECA RG, ATMACA-SONMEZ P et al.: Retinal pigment epithelium damage enhances expression of chemoattractants and migration of bone marrow-derived stem cells. Invest. Ophthalmol. Vis. Sci. (2006) 47(4):1646-1652.
  • AIUTI A, WEBB IJ, BLEUL C, SPRINGER T, GUTIERREZ-RAMOS JC: The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J. Exp. Med. (1997) 185(1):111-112.
  • DAS AV, MALLYA KB, ZHAO X et al.: Neural stem cell properties of Muller glia in the mammalian retina: regulation by Notch and Wnt signaling. Dev. Biol. (2006) 299(1):283-302.
  • EL-BRADEY M, CHENG L, BARTSCH DU et al.: Preventive versus treatment effect of AG3340, a potent matrix metalloproteinase inhibitor in a rat model of choroidal neovascularization. J. Ocul. Pharmacol. Ther. (2004) 20(3):217-236.
  • EL-BRADEY M, CHENG L, BARTSCH DU, NIESSMAN M, EL-MUSHARAF A, FREEMAN WR: The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinase, on a new animal model of epiretinal membrane. Retina (2004) 24(5):783-789.
  • PENN RJ, RAJARATNAM VS: Inhibition of retinal neovascularization by intravitreal injection of human rPAI-1 in a rat model of retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. (2003) 44(12):5423-5429.
  • PAN H, NGUYEN NQ, YOSHIDA H et al.: Molecular targeting of antiangiogenic factor 16K hPRL inhibits oxygen-induced retinopathy in mice. Invest. Ophthalmol. Vis. Sci. (2004) 45(7):2413-2419.
  • BUTLER JM, GUTHRIE SM, KOC M et al.: SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J. Clin. Invest. (2005) 115(1):86-93.
  • RIECKE B, CHAVAKIS E, BRETZEL RG et al.: Topical application of integrin antagonists inhibits proliferative retinopathy. Horm. Metab. Res. (2001) 33(5):307-311.
  • 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. (2002): 43(3):821-829.
  • ZHANG SX, WANG JJ, GAO G, SHAO C, MOTT R, MA JX: Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor. FASEB J. (2006) 20(2):323-332.
  • DRIXLER TA, BOREL RINKES IH, RITCHIE ED et al.: Angiostatin inhibits pathological but not physiological retinal angiogenesis. Invest. Ophthalmol. Vis. Sci. (2001) 42(13):3325-3330.
  • SIMA J, ZHANG SX, SHAO C, FANT J, MA JX: The effect of angiostatin on vascular leakage and VEGF expression in rat retina. FEBS Lett. (2004) 564(1-2):19-23.
  • ZHANG D, KAUFMAN PL, GAO G, SAUNDERS RA, MA JK: Intravitreal injection of plasminogen kringle 5, an endogenous angiogenic inhibitor, arrests retinal neovascularization in rats. Diabetologia (2001) 44(6):757-765.
  • ZHANG SX, SIMA J, SHAO C et al.: Plasminogen kringle 5 reduces vascular leakage in the retina in rat models of oxygen-induced retinopathy and diabetes. Diabetologia (2004) 47(1):124-131.
  • BAINBRIDGE JW, MISTRY A, DE ALWIS M et al.: Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther. (2002) 9(5):320-326.
  • LAI YK, SHEN WY, BRANKOV M, LAI CM, CONSTABLE IJ, RAKOCZY PE: Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy. Gene Ther. (2002) 9(12):804-813.
  • GELHBACH P, DEMETRIADES AM, YAMAMOTO S et al.: Periocular gene transfer of sFlt-1 suppresses ocular neovascularization and vascular endothelial growth factor-induced breakdown of the blood–retinal barrier. Hum. Gene Ther. (2003) 20(2):129-141.
  • LAI CM, SHEN WY, BRANKOW M et al.: Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys. Mol. Ther. (2005) 12(4):659-668.
  • BAINBRIDGE JW, JIA A, BAGHERZADEH A, SELWOOD D, ALI RR, ZACHARY I: A peptide encoded by exon 6 of VEGF (EG3306) inhibits VEGF-induced angiogenesis in vitro and ischaemic retinal neovascularisation in vivo. Biochem. Biophys. Res. Commun. (2003) 302(4):793-799.
  • DENG WT, YAN Z, DINCULESCU A et al.: Adeno-associated virus-mediated expression of vascular endothelial growth factor peptides inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. Hum. Gene Ther. (2005) 16(11):1247-1254.
  • IKUNO Y, KAZLAUSKAS A: An in vivo gene therapy approach for experimental proliferative vitreoretinopathy using the truncated platelet-derived growth factor α receptor. Invest. Ophthalmol. Vis. Sci. (2002) 43(7):2406-2411.
  • OSHIMA Y, SAKAMOTO, HISATOMI, TSUTSUMI C, UENO H, ISHIBASHI T: Gene transfer of soluble TGF-β type II receptor inhibits experimental proliferative vitreoretinopathy. Gene Ther. (2002) 9(18):1214-1220.
  • RAISLER BJ, BERNS KI, GRANT MB, BELIAEV D, HAUSWIRTH WW: Adeno-associated virus type-2 expression of pigmented epithelium-derived factor or Kringles 1-3 of angiostatin reduce retinal neovascularization. Proc. Natl. Acad. Sci. USA (2002) 99(13):8909-8914.
  • AURICCHIO A, BEHLING KC, MAGUIRE AM et al.: Inhibition of retinal neovascularization by intraocular viral-mediated delivery of antiangiogenic agents. Mol. Ther. (2002) 6(4):490-494.
  • MORI K, ANDO A, GEHLBACH P et al.: Inhibition of choroidal neovascularization by intravenous injection of adenoviral vectors expressing secretable endostatin. Am. J. Pathol. (2001) 159(1):313-320.
  • GEHLBACH P, DEMETRIADES AM, YAMAMOTO S et al.: Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization. Gene Ther. (2003) 10(8):637-646.
  • SAISHIN Y, SILVA RL, SAISHIN Y et al.: Periocular gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization in a human-sized eye. Hum. Gene Ther. (2005) 16(4):473-478.
  • TAKAHASHI K, SAISHIN Y, SAISHIN Y et al.: Intraocular expression of endostatin reduces VEGF-induced retinal vascular permeability, neovascularization, and retinal detachment. FASEB J. (2003) 17(8):896-898.
  • BALAGGAN KS, BILEY K, ESAPA M et al.: EIAV vector-mediated delivery of endostatin or angiostatin inhibits angiogenesis and vascular hyperpermeability in experimental CNV. Gene Ther. (2006) 13(15):1153-1165.
  • LAI CC, WU WC, CHEN SL et al.: Suppression of choroidal neovascularization by adeno-associated virus vector expressing angiostatin. Invest. Ophthalmol. Vis. Sci. (2001) 42(10):2401-2407.
  • IGARASHI T, MIYAKE K, KATO K et al.: Lentivirus-mediated expression of angiostatin efficiently inhibits neovascularization in a murine proliferative retinopathy model. Gene Ther. (2003) 10(3):219-226.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.