VEGF antagonism and age-related macular degeneration: too much of a good thing?

References

• 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).
   PubMed Web of Science ®Google Scholar
• 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).
   PubMed Web of Science ®Google Scholar
• 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).
   PubMed Web of Science ®Google Scholar
• 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).
   PubMed Web of Science ®Google Scholar
• 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).
   PubMed Web of Science ®Google Scholar
• Ishida S, Usui T, Yamashiro K et al. VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J. Exp. Med. 198(3), 483–489 (2003).
   PubMed Web of Science ®Google Scholar
• 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).
   PubMed Web of Science ®Google Scholar
• Takeda AL, Colquitt J, Clegg AJ, Jones J. Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review. Br. J. Ophthalmol. 91(9), 1177–1182 (2007).
   PubMed Web of Science ®Google Scholar
• Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 15(2), 171–185 (2012).
   PubMed Web of Science ®Google Scholar
• Ferrara N, Carver-Moore K, Chen H et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573), 439–442 (1996).
   PubMed Web of Science ®Google Scholar
• Carmeliet P, Ferreira V, Breier G et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573), 435–439 (1996).
   PubMed Web of Science ®Google Scholar
• Marneros AG, Fan J, Yokoyama Y et al. Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am. J. Pathol. 167(5), 1451–1459 (2005).
   PubMed Web of Science ®Google Scholar
• Le YZ, Bai Y, Zhu M, Zheng L. Temporal requirement of RPE-derived VEGF in the development of choroidal vasculature. J. Neurochem. 112(6), 1584–1592 (2010).
   PubMed Web of Science ®Google Scholar
• Kurihara T, Westenskow PD, Bravo S, Aguilar E, Friedlander M. Targeted deletion of VEGFa in adult mice induces vision loss. J. Clin. Invest. 122(11), 4213–4217 (2012).
   PubMed Web of Science ®Google Scholar
• 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. USA 106(44), 18751–18756 (2009).
   PubMed Web of Science ®Google Scholar
• Robinson GS, Ju M, Shih SC et al. Nonvascular role for VEGF: VEGFR-1, 2 activity is critical for neural retinal development. FASEB J. 15(7), 1215–1217 (2001).
   PubMed Web of Science ®Google Scholar
• Nishijima K, Ng YS, Zhong L et al. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am. J. Pathol. 171(1), 53–67 (2007).
   PubMed Web of Science ®Google Scholar
• Saint-Geniez M, Maharaj AS, Walshe TE et al. Endogenous VEGF is required for visual function: evidence for a survival role on Müller cells and photoreceptors. PLoS ONE 3(11), e3554 (2008).
   PubMed Web of Science ®Google Scholar
• Cvetanovic M, Patel JM, Marti HH, Kini AR, Opal P. Vascular endothelial growth factor ameliorates the ataxic phenotype in a mouse model of spinocerebellar ataxia type 1. Nat. Med. 17(11), 1445–1447 (2011).
   PubMed Web of Science ®Google Scholar
• Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc. Natl Acad. Sci. USA 99(18), 11946–11950 (2002).
   PubMed Web of Science ®Google Scholar
• Pedersen KB, Møller F, Sjølie AK, Andréasson S. Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration. Retina (Philadelphia, PA) 30(7), 1025–1033 (2010).
   PubMed Web of Science ®Google Scholar
• Martin DF, Maguire MG, Fine SL et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmol. 119(7), 1388–1398 (2012).
   PubMed Web of Science ®Google Scholar
• Rosenfeld PJ, Shapiro H, Tuomi L, Webster M, Elledge J, Blodi B. Characteristics of patients losing vision after 2 years of monthly dosing in the Phase III ranibizumab clinical trials. Ophthalmol. 118(3), 523–530 (2011).
   PubMed Web of Science ®Google Scholar
• 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).
   PubMed Web of Science ®Google Scholar
• Eremina V, Jefferson JA, Kowalewska J et al. VEGF inhibition and renal thrombotic microangiopathy. N. Engl. J. Med. 358(11), 1129–1136 (2008).
   PubMed Web of Science ®Google Scholar
• Eremina V, Sood M, Haigh J et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J. Clin. Invest. 111(5), 707–716 (2003).
   PubMed Web of Science ®Google Scholar
• Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br. J. Cancer 96(12), 1788–1795 (2007).
   PubMed Web of Science ®Google Scholar
• Sung HK, Doh KO, Son JE et al. Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab. 17(1), 61–72 (2013).
   PubMed Web of Science ®Google Scholar