975
Views
34
CrossRef citations to date
0
Altmetric
REVIEW ARTICLE

Vascular endothelial growth factors in retinal and choroidal neovascular diseases

&
Pages 1-17 | Received 26 May 2010, Accepted 21 Sep 2010, Published online: 01 Feb 2011

References

  • Alm A. Ocular circulation. Hart WM. Adler's Physiology of the Eye. St Louis, USA: Mosby Year Book; 1992. 198–227.
  • Folkman J, Ingber D. Inhibition of angiogenesis. Semin Cancer Biol. 1992;3:89–96.
  • WHO. Prevent from blindness, WHO report 9–11 November 2005.
  • Smith W, Assink J, Klein R, Mitchell P, Klaver CCW, Klein BEK, . Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology. 2001;108:697–704.
  • Senger D, Galli S, Dvorak A, Perruzzi C, Harvey V, Dvorak H. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219: 983–5.
  • Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, . Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci U S A. 1996;93:2576–81.
  • Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico M. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci U S A. 1991;88:9267–71.
  • Joukov V, Kaipainen A, Jeltsch M, Pajusola K, Olofsson B, Kumar V, . Vascular endothelial growth factors VEGF-B and VEGF-C. J Cell Physiol. 1997;173:211–5.
  • Achen M, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks A, . Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci U S A. 1998; 95:548–53.
  • Yamazaki Y, Takani K, Atoda H, Morita T. Snake venom vascular endothelial growth factors (VEGFs) exhibit potent activity through their specific recognition of KDR (VEGF Receptor 2). J Biol Chem. 2003;278:51985–8.
  • Ogawa S, Oku A, Sawano A, Yamaguchi S, Yazaki Y, Shibuya M. A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. J Biol Chem. 1998;273: 31273–82.
  • Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW. The vascular endothelial growth factor family of polypeptides. J Cell Biochem. 1991;47:211–8.
  • Senger DR, Connolly DT, Van De Water L, Feder J, Dvorak HF. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res. 1990;50:1774–8.
  • Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, . Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435–9.
  • 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. 1995;72:638–45.
  • 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. 1996;114:1210–7.
  • Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, . Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331:1480–7.
  • 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. 2002;133: 70–7.
  • Young TL, Anthony DC, Pierce E, Foley E, Smith LE. Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J AAPOS. 1997;1:105–10.
  • Kvanta A, Algvere P, Berglin L, Seregard S. Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1996;37:1929–34.
  • Kim I, Ryan A, Rohan R, Amano S, Agular S, Miller J, . Constitutive expression of VEGF, VEGFR-1, and VEGFR-2 in normal eyes. Invest Ophthalmol Vis Sci. 1999;40:2115–21.
  • Ferrara N, Gerber H, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.
  • Akiyama H, Mohamedali KA, E Silva RL, Kachi S, Shen J, Hatara C, . Vascular targeting of ocular neovascularization with a vascular endothelial growth factor121/gelonin chimeric protein. Mol Pharmacol. 2005;68:1543–50.
  • Saint-Geniez M, Maldonado AE, D'Amore PA. VEGF expression and receptor activation in the choroid during development and in the adult. Invest Ophthalmol Vis Sci. 2006;47:3135–42.
  • Shima DT, Nishijima K, Jo N, Adamis AP. VEGF-mediated neuroprotection in ischemic retina. Invest Ophthalmol Vis Sci. 2004;45:3270.
  • Alon T, Hemo I, Itin A, Pe'er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med. 1995;1:1024–8.
  • Yi X, Mai L, Uyama M, Yew DTW. Time-course expression of vascular endothelial growth factor as related to the development of the retinochoroidal vasculature in rats. Exp Brain Res. 1998;118:155–60.
  • Peters S, Heiduschka P, Julien S, Ziemssen F, Fietz H, Bartz-Schmidt KU, . Ultrastructural findings in the primate eye after intravitreal injection of bevacizumab. Am J Ophthalmol. 2007;143:995–1002.
  • Reichelt M, Shi S, Hayes M, Kay G, Batch J, Gole GA, . Vascular endothelial growth factor-B and retinal vascular development in the mouse. Clin Experiment Ophthalmol. 2003;31:61–5.
  • Joukov V, Sorsa T, Kumar V, Jeltsch M, Claesson-Welsh L, Cao Y, . Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J. 1997;16:3898–911.
  • Cao Y, Linden P, Farnebo J, Cao R, Eriksson A, Kumar V, . Vascular endothelial growth factor C induces angiogenesis in vivo. Proc Natl Acad Sci U S A. 1998;95:14389–94.
  • Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, . Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276:1423–5.
  • Ikeda Y, Yonemitsu Y, Onimaru M, Nakano T, Miyazaki M, Kohno R, . The regulation of vascular endothelial growth factors (VEGF-A, -C, and -D) expression in the retinal pigment epithelium. Exp Eye Res. 2006;83:1031–40.
  • Kinnunen K, Puustjarvi T, Terasvirta M, Nurmenniemi P, Heikura T, Laidinen S, . Differences in retinal neovascular tissue and vitreous humour in patients with type 1 and type 2 diabetes. Br J Ophthalmol. 2009;93:1109–15.
  • Ohno-Matsui K, Yoshida T, Uetama T, Mochizuki M, Morita I. Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells. Biochem Biophys Res Commun. 2003;303:962–7.
  • Khaliq A, Foreman D, Ahmed A, Weich H, Gregor Z, McLeod D, . Increased expression of placenta growth factor in proliferative diabetic retinopathy. Lab Invest. 1998;78: 109–16.
  • Terman BI, Dougher-Vermazen M, Carrion ME, Dimitrov D, Armellino DC, Gospodarowicz D, . Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun. 1992;187: 1579–86.
  • Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998;92:735–45.
  • Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 1995;376:66–70.
  • Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, . Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995; 376:62–6.
  • Blaauwgeers HGT, Holtkamp GM, Rutten H, Witmer AN, Koolwijk P, Partanen TA, . Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris: evidence for a trophic paracrine relation. Am J Pathol. 1999;155: 421–8.
  • Gille H, Kowalski J, Li B, LeCouter J, Moffat B, Zioncheck TF, . Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem. 2001;276:3222–30.
  • Lahteenvuo JE, Lahteenvuo MT, Kivela A, Rosenlew C, Falkevall A, Klar J, . Vascular endothelial growth factor-b induces myocardium-specific angiogenesis and arteriogenesis via vascular endothelial growth factor receptor-1- and neuropilin receptor-1-dependent mechanisms. Circulation. 2009;119:845–56.
  • Herzog Y, Kalcheim C, Kahane N, Reshef R, Neufeld G. Differential expression of neuropilin-1 and neuropilin-2 in arteries and veins. Mech Dev. 2001;109:115–9.
  • Shen J, Samul R, Zimmer J, Liu H, Liang X, Hackett S, . Deficiency of neuropilin 2 suppresses VEGF-induced retinal neovascularization. Mol Med. 2004;10:12–18.
  • Oh H, Takagi H, Otani A, Koyama S, Kemmochi S, Uemura A, . Selective induction of neuropilin-1 by vascular endothelial growth factor (VEGF): A mechanism contributing to VEGF-induced angiogenesis. Proc Natl Acad Sci U S A. 2002;99:383–8.
  • Ishida S, Shinoda K, Kawashima S, Oguchi Y, Okada Y, Ikeda E. Coexpression of VEGF receptors VEGF-R2 and neuropilin-1 in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2000;41:1649–56.
  • He Y, Smith SK, Day KA, Clark DE, Licence DR, Charnock-Jones DS. Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre-mRNA is important for the regulation of VEGF activity. Mol Endocrinol. 1999;13:537–45.
  • Kendall RL, Wang G, Thomas KA. Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun. 1996;226:324–8.
  • Honda M, Sakamoto T, Ishibashi T, Inomata H, Ueno H. Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration. Gene Ther. 2000;7:978–85.
  • Daley ML, Watzke RC, Riddle MC. Early loss of blue-sensitive color vision in patients with type I diabetes. Diabetes Care. 1987;10:777–81.
  • Speiser P, Gittelsohn AM, Patz A. Studies on diabetic retinopathy. 3. Influence of diabetes on intramural pericytes. Arch Ophthalmol. 1968;80:332–7.
  • Miyamoto K, Ogura Y. Pathogenetic potential of leukocytes in diabetic retinopathy. Semin Ophthalmol. 1999;14:233–9.
  • Hammes H, Lin J, Renner O, Shani M, Lundqvist A, Betsholtz C, . Pericytes and the pathogenesis of diabetic retinopathy. Diabetes. 2002;51:3107–12.
  • Li W, Liu X, Yanoff M, Cohen S, Ye X. Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from high to low glucose levels: a comparative study with retinal capillary endothelial cells. Diabetologia. 1996; 39:537–47.
  • Zheng L, Szabo C, Kern TS. Poly(ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-kappaB. Diabetes. 2004;53: 2960–7.
  • Kowluru RA, Koppolu P, Chakrabarti S, Chen S. Diabetes-induced activation of nuclear transcriptional factor in the retina, and its inhibition by antioxidants. Free Radic Res. 2003;37:1169–80.
  • Gabbay KH. Hyperglycemia, polyol metabolism, and complications of diabetes mellitus. Annu Rev Med. 1975;26: 521–36.
  • Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med. 1984;101:527–37.
  • Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996;19: 257–67.
  • Taher MM, Garcia JG, Natarajan V. Hydroperoxide-induced diacylglycerol formation and protein kinase C activation in vascular endothelial cells. Arch Biochem Biophys. 1993;303:260–6.
  • Inoguchi T, Battan R, Handler E, Sportsman J, Heath W, King G. Preferential elevation of protein kinase c isoform {beta}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 U S A. 1992;89: 11059–63.
  • Aiello LP, Clermont A, Arora V, Davis MD, Sheetz MJ, Bursell S. Inhibition of PKC {beta} by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients. Invest Ophthalmol Vis Sci. 2006;47:86–92.
  • Paques M, Massin P, Gaudric A. Growth factors and diabetic retinopathy. Diabetes Metab. 1997;23:125–30.
  • Vinores SA, Youssri AI, Luna JD, Chen YS, Bhargave S, Vinores MA, . Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease. Histol Histopathol. 1997;12:99–109.
  • Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial. Branch Vein Occlusion Study Group. Arch Ophthalmol. 1986;104:34–41.
  • Pierce E, Avery R, Foley E, Aiello L, Smith L. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci U S A. 1995;92:905–9.
  • Pe'er J, Folberg R, Itin A, Gnessin H, Hemo I, Keshet E. Vascular endothelial growth factor upregulation in human central retinal vein occlusion. Ophthalmology. 1998;105: 412–6.
  • Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, . Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol. 2005; 140:256–61.
  • Terry TL. Fibroblastic overgrowth of persistent tunica vasculosa lentis in infants born prematurely: II. Report of cases—clinical aspects. Trans Am Ophthalmol Soc. 1942; 40:262–84.
  • Seiberth V, Linderkamp O. Risk factors in retinopathy of prematurity. A multivariate statistical analysis. Ophthalmologica. 2000;214:131–5.
  • An international classification of retinopathy of prematurity. II. The classification of retinal detachment. The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity. Arch Ophthalmol. 1987;105:906–12.
  • Ashton N, Ward B, Serpell G. Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. Br J Ophthalmol. 1954;38:397–432.
  • Chan-Ling T, Tout S, Hollander H, Stone J. Vascular changes and their mechanisms in the feline model of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 1992;33: 2128–47.
  • Smith L, Wesolowski E, McLellan A, Kostyk S, D'Amato R, Sullivan R, . Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35:101–11.
  • Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP. Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol. 2003;48:257–93.
  • Dunaief JL, Dentchev T, Ying G, Milam AH. The role of apoptosis in age-related macular degeneration. Arch Ophthalmol. 2002;120:1435–42.
  • Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102:1640–2.
  • Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration. Macular Photocoagulation Study Group. Arch Ophthalmol. 1997;115:741–7.
  • Frennesson C, Nilsson UL, Nilsson SE. Colour contrast sensitivity in patients with soft drusen, an early stage of ARM. Doc Ophthalmol. 1995;90:377–86.
  • Midena E, Segato T, Blarzino MC, Degli Angeli C. Macular drusen and the sensitivity of the central visual field. Doc Ophthalmol. 1994;88:179–85.
  • Anderson DH, Ozaki S, Nealon M, Neitz J, Mullins RF, Hageman GS, . Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation. Am J Ophthalmol. 2001;131:767–81.
  • Hageman G, Mullins R, Russell S, Johnson L, Anderson D. Vitronectin is a constituent of ocular drusen and the vitronectin gene is expressed in human retinal pigmented epithelial cells. FASEB J. 1999;13:477–84.
  • Hee MR, Baumal CR, Puliafito CA, Duker JS, Reichel E, Wilkins JR, . Optical coherence tomography of age-related macular degeneration and choroidal neovascularization. Ophthalmology. 1996;103:1260–70.
  • Risk factors associated with age-related macular degeneration: A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. Age-Related Eye Disease Study Research Group. Ophthalmology. 2000;107:2224–32.
  • Curcio CA, Millican CL. Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch Ophthalmol. 1999;117:329–39.
  • Bressler NM, Silva JC, Bressler SB, Fine SL, Green WR. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. Retina. 1994;14:130–42.
  • Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85:845–81.
  • Kennedy CJ, Rakoczy PE, Constable IJ. Lipofuscin of the retinal pigment epithelium: a review. Eye. 1995;9:763–71.
  • Sundelin S, Wihlmark U, Nilsson SE, Brunk UT. Lipofuscin accumulation in cultured retinal pigment epithelial cells reduces their phagocytic capacity. Curr Eye Res. 1998;17:851–7.
  • Delori FC, Goger DG, Dorey CK. Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Invest Ophthalmol Vis Sci. 2001;42:1855–66.
  • Holz F, Schutt F, Kopitz J, Eldred G, Kruse F, Volcker H, . Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci. 1999;40:737–43.
  • Boulton M, Dontsov A, Jarvis-Evans J, Ostrovsky M, Svistunenko D. Lipofuscin is a photoinducible free radical generator. J Photochem Photobiol B. 1993;19:201–4.
  • Penfold PL, Killingsworth MC, Sarks SH. Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol. 1985;223:69–76.
  • Killingsworth MC, Sarks JP, Sarks SH. Macrophages related to Bruch's membrane in age-related macular degeneration. Eye. 1990;4:613–21.
  • Oh H, Takagi H, Takagi C, Suzuma K, Otani A, Ishida K, . The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes. Invest Ophthalmol Vis Sci. 1999;40:1891–8.
  • Green WR, Key SN 3rd. Senile macular degeneration: a histopathologic study. 1977. Retina. 2005;25:180–250.
  • Chong NHV, Keonin J, Luthert PJ, Frennesson CI, Weingeist DM, Wolf RL, . Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration. Am J Pathol. 2005;166: 241–51.
  • Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong, PT. Increased expression of angiogenic growth factors in age-related maculopathy. Br J Ophthalmol. 1997;81:154–62.
  • Wells JA, Murthy R, Chibber R, Nunn A, Molinatti PA, Kohner EM, . Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation. Br J Ophthalmol. 1996;80:363–6.
  • Lip P, Blann AD, Hope-Ross M, Gibson JM, Lip GYH. Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction. Ophthalmology. 2001;108:705–10.
  • D'Amico DJ. Pegaptanib sodium for neovascular age- related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology. 2006;113:992–1001.
  • Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.
  • Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V. Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci. 2005; 46:726–33.
  • Drolet D, Nelson J, Tucker C, Zack P, Nixon K, Bolin R, . Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys. Pharm Res. 2000;17:1503–10.
  • Adamis AP, Altaweel M, Bressler NM, Cunningham ET Jr, Davis MD, Goldbaum M, . Macugen Diabetic Retinopathy Study Group. Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology. 2006;113:23–8.
  • Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, . Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–31.
  • Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, . Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432–44.
  • Antoszyk AN, Tuomi L, Chung CY, Singh A. Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): Year 2 results. Am J Ophthalmol. 2008;145:862–74.
  • Singer M, Wong P, Wang P, Scott L. HORIZON Extension Trial of Ranibizumab (LUCENTIS®) for Neovascular Age-Related Macular Degeneration (AMD): Two-year safety and efficacy results. Invest Ophthalmol Vis Sci. 2009;50:3093.
  • Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, . Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 1. Am J Ophthalmol. 2008;145:239–48.
  • Lalwani GA, Rosenfeld PJ, Fung AE, Dubovy SR, Michels S, Feuer W, . A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: Year 2 of the PrONTO Study. Am J Ophthalmol. 2009; 148:43–58.
  • Adepegba OA, Gupta B, Adewoyin T, Patel S, Sivaprasad S. Comparison of two treatment schedules of intravitreal ranibizumab for neovascular age related macular degeneration. Invest Ophthalmol Vis Sci. 2010;51:71.
  • Nguyen QD, Shah SM, Heier JS, Do DV, Lim J, Boyer D, . Primary end point (six months) results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study. Ophthalmology. 2009;116:2175–81.
  • Ho AC, Gray S, Rundle A, Li Z, Yee Murahashi W, Rubio R, . Ranibizumab in patients with macular edema following retinal vein occlusion: 12-month outcomes of BRAVO and CRUISE. Invest Ophthalmol Vis Sci. 2010;51:6452.
  • Schmidt-Erfurth UM, Pruente C. Management of neovascular age-related macular degeneration. Prog Retin Eye Res. 2007;26:437–51.
  • Spaide RF, Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA, . Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina. 2006;26:383–90.
  • Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, . Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology. 2006;113:1695–705.
  • Spaide RF, Fisher YL. Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage. Retina. 2006;26:275–8.
  • Kreutzer TC, Alge CS, Wolf AH, Kook D, Burger J, Strauss R, . Intravitreal bevacizumab for the treatment of macular oedema secondary to branch retinal vein occlusion. Br J Ophthalmol. 2008;92:351–5.
  • Stahl A, Agostini H, Hansen L, Feltgen N. Bevacizumab in retinal vein occlusion-results of a prospective case series. Graefes Arch Clin Exp Ophthalmol. 2007;245:1429–36.
  • Kong L, Mintz-Hittner HA, Penland RL, Kretzer FL, Chevez-Barrios P. Intravitreous bevacizumab as anti-vascular endothelial growth factor therapy for retinopathy of prematurity: a morphologic study. Arch Ophthalmol. 2008;126: 1161–3.
  • Saishin Y, Saishin Y, Takahashi K, Lima e Silva R, Hylton D, Rudge JS, . VEGF-TRAP(R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier. J Cell Physiol. 2003;195:241–8.
  • Nguyen QD, Shah SM, Browning DJ, Hudson H, Sonkin P, Hariprasad SM, . A phase I study of intravitreal vascular endothelial growth factor trap-eye in patients with neovascular age-related macular degeneration. Ophthalmology. 2009; 116:2141–8.
  • Major JC Jr, Brown DM; DA VINCI Study Group. DA VINCI: DME and VEGF Trap-Eye: INvestigation of Clinical Impact: Phase 2 Study in patients with diabetic macular edema (DME). Invest Ophthalmol Vis Sci. 2010;51:6426.
  • Reich SJ, Fosnot J, Kuroki A, Tang W, Yang X, Maguire AM, . Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol Vis. 2003;9:210–6.
  • Tolentino MJ, Brucker AJ, Fosnot J, Ying GS, Wu IH, Malik G, . Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal neovascularization. Retina. 2004;24:660.
  • Shen J, Samul R, Silva RL, Akiyama H, Liu H, Saishin Y, . Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Ther. 2006;13:225–34.
  • Kleinman ME, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi JZ, . Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature. 2008;452:591–7.
  • Fang AM, Lee AY, Kulkarni M, Osborn MP, Brantley MA Jr. Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration. Mol Vis. 2009; 15:2710–9.
  • Abhary S, Burdon KP, Gupta A, Lake S, Selva D, Petrovsky N, . Common sequence variation in the VEGFA gene predicts risk of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2009;50:5552–8.
  • Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 1992;12:5447–54.
  • Boyer DS; Ophthotech Anti-PDGF in AMD Study Group. Combined inhibition of platelet derived (PDGF) and vascular endothelial (VEGF) growth factors for the treatment of neovascular age-related macular degeneration (NV-AMD)—results of a phase 1 study. Invest Ophthalmol Vis Sci. 2009; 50:1260.
  • Takagi H, Koyama S, Seike H, Oh H, Otani A, Matsumura M, . Potential role of the angiopoietin/Tie2 system in ischemia-induced retinal neovascularization. Invest Ophthalmol Vis Sci. 2003;44:393–402.
  • Apte RS; Ophthotech Anti-Complement in AMD Study Group. Targeting complement factor 5 in neovascular age-related macular degeneration (NV-AMD)—Results of a Phase 1 Study. Invest Ophthalmol Vis Sci. 2009;50:5011.
  • Zahn G, Vossmeyer D, Stragies R, Wills M, Wong CG, Loffler KU, . Preclinical evaluation of the novel small-molecule integrin {alpha}5{beta}1 inhibitor JSM6427 in monkey and rabbit models of choroidal neovascularization. Arch. Ophthalmol. 2009;127:1329–35.
  • Avery RL. Extrapolating anti-vascular endothelial growth factor therapy into pediatric ophthalmology: Promise and concern. J AAPOS. 2009;13:329–31.
  • Saint-Geniez M, Maharaj ASR, Walshe TE, Tucker BA, Sekiyama E, Kurihara T, . Endogenous VEGF is required for visual function: evidence for a survival role on müller cells and photoreceptors. PLoS ONE. 2008; 3:e3554.
  • Saint-Geniez M, Kurihara T, Sekiyama E, Maldonado AE, D'Amore PA. An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris. Proc Natl Acad Sci U S A. 2009;106:18751–6.

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.