title: Expression and role of VEGF in the adult retinal pigment epithelium.
abstract: OBJECTIVE
  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. VEGF blockade is a widely used treatment for neovascular diseases such as wet age-related macular degeneration (AMD). Therefore, it was sought in this study to evaluate the expression and role of endogenous VEGF in RPE.
  
  
  METHODS
  VEGF and VEGFR2 expression in the murine retina were assessed during development. 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 was systemically neutralized in vivo by adenoviral-mediated overexpression of soluble VEGFR1 (sFlt). RPE and choriocapillaris were analyzed by transmission electron microscopy (TEM). Changes in gene expression were evaluated by quantitative real-time PCR.
  
  
  RESULTS
  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. VEGF neutralization in vitro led to increased apoptosis and reduced microvilli density and length. Systemic VEGF neutralization led to transient degenerative changes; RPE were vacuolated and separated from photoreceptor outer segments, and choriocapillaris fenestrations were decreased. 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.
  
  
  CONCLUSIONS
  These results indicate that VEGF plays a critical role in survival and maintenance of RPE integrity. Potential undesired off-target effects should be considered with chronic use of anti-VEGF agents.
authors: Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors: Knatokie M
authors: KM
authors: Ford
authors: Magali
authors: M
authors: Saint-Geniez
authors: Tony
authors: T
authors: Walshe
authors: Alisar
authors: A
authors: Zahr
authors: Patricia A
authors: PA
authors: D'Amore
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D017348:Microscopy, Electron, Scanning Transmission; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics*; D055213:Retinal Pigment Epithelium / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2