![]() ![]() Potential undesired off-target effects should be considered with chronic use of anti-VEGF agents. These results indicate that VEGF plays a critical role in survival and maintenance of RPE integrity. VEGF levels were elevated in RPE of Ad-sFlt1 mice at day 4 postinfection, and there was increased expression of the neurotrophic factor CD59a at day 14. Systemic VEGF neutralization led to transient degenerative changes RPE were vacuolated and separated from photoreceptor outer segments, and choriocapillaris fenestrations were decreased. VEGF neutralization in vitro led to increased apoptosis and reduced microvilli density and length. VEGF expression was detected in the developing RPE as early as embryonic day (E) 9.5, whereas VEGFR2 expression by RPE began nonuniformly between postnatal (P) day 6.5 and P8.5. Purpose: Vascular endothelial growth factor (VEGF) and its receptor VEGFR2 are promising therapeutic targets for wet age-related macular degeneration (AMD). ![]() Changes in gene expression were evaluated by quantitative real-time PCR. RPE and choriocapillaris were analyzed by transmission electron microscopy (TEM). VEGF was systemically neutralized in vivo by adenoviral-mediated overexpression of soluble VEGFR1 (sFlt). Bevacizumab was used to neutralize VEGF in ARPE-19 cells, and the effects on cell survival and apical microvill were assessed by TUNEL and SEM, respectively. VEGF and VEGFR2 expression in the murine retina were assessed during development. Therefore, it was sought in this study to evaluate the expression and role of endogenous VEGF in RPE. VEGF blockade is a widely used treatment for neovascular diseases such as wet age-related macular degeneration (AMD). Despite a lack of active angiogenesis, VEGF is expressed in nearly every adult tissue, and recent evidence suggests that VEGF may serve as a survival factor for both vascular and nonvascular tissues. ![]()
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