title: Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an american ophthalmological society thesis).
abstract: OBJECTIVE
  To study vascular endothelial growth factor (VEGF) regulation in the development of intravitreous neovascularization and peripheral avascular retina in peripheral severe retinopathy of prematurity (ROP).
  
  
  METHODS
  The rat 50/10 model of ROP mimics zone II, stage 3 severe ROP and recreates fluctuations in transcutaneous oxygen levels in preterm infants. On postnatal (p) day ages p0, p8, p11-p14, and p18, retinas from the model or room-air (RA) age-matched pups were analyzed for mRNA of VEGF splice variants and receptors using real-time polymerase chain reaction or VEGF protein using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  On p14, when retinas were only 70% vascularized in the model but fully vascularized in RA, VEGF₁₆₄ expression was threefold greater in the model compared to RA. On p18, intravitreous neovascularization was associated with a 5-fold increase in VEGF₁₆₄ mRNA in the model compared to RA. By analysis of variance, VEGF₁₆₄ and VEGFR2 mRNAs were up-regulated in association with increasing developmental age (P<.0001 for both comparisons) or exposure to the model compared to RA (P<.0001 and P=.0247, respectively), whereas increasing developmental age was associated only with up-regulated VEGF₁₂₀ (P=.0006), VEGF₁₈₈ (P=.0256), and VEGFR1 (P<.0001) mRNAs. VEGF protein increased significantly in the model and on p14 and p18 compared to RA (P<.0001).
  
  
  CONCLUSIONS
  The model mimics contemporary severe ROP in the United States unlike other models of oxygen-induced retinopathy. Compared to RA retinas, VEGF significantly increased in association with avascular retina and intravitreous neovascularization. A hypothesis is proposed that VEGF up-regulation plays a role in the development of both important features.
authors.affiliation: Moran Eye Center, University of Utah, Salt Lake City, USA.
authors.forename: Mary Elizabeth
authors.initials: ME
authors.lastname: Hartnett
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D017679:Cryotherapy; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D053685:Laser Therapy; D054835:Lipocalin 1 / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000378:metabolism; D047928:Premature Birth; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D012164:Retinal Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D012171:Retinal Vessels / Q000002:abnormalities*; D012720:Severity of Illness Index; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014822:Vitreous Body / Q000098:blood supply*
chemical_list: C518449:Lcn1 protein, rat; D054835:Lipocalin 1; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C518453:Vegp2 protein, rat; C467498:vascular endothelial growth factor A, rat