Association of retinal vascular endothelial growth factor with avascular retina in a rat model of retinopathy of prematurity.
OBJECTIVE
To study the effects of oxygen fluctuations on rat vascular endothelial growth factor (VEGF), VEGF receptor 1(VEGFR1), and VEGFR2 in a model of retinopathy of prematurity (ROP).


METHODS
Retinas at several postnatal days (p) were analyzed for VEGF splice variants, VEGFR1 and VEGFR2 messenger RNAs (mRNAs) using real-time polymerase chain reaction or for VEGF protein using enzyme-linked immunosorbent assay.


RESULTS
Older developmental age was associated with VEGFR1 (P < .001), VEGF(120) (P < .001), and VEGF(188) (P = .03) mRNA overexpression. Expression of VEGFR2 and VEGF(164) mRNAs were associated with older age (P < .001) or exposure to the ROP model (P = .02 and P < .001, respectively). Expression of VEGF protein was greater at p14, when 30% avascular retina existed in the ROP model, compared with room air, when no avascular retina existed, and at p18, when intravitreous neovascularization existed in the model but not in room air (P < .001 for both).


CONCLUSIONS
Unlike models of oxygen-induced retinopathy that describe ROP before implementation of oxygen regulation, the ROP model re-creates oxygen stresses relevant to preterm infants with severe ROP today. Expression of VEGF(164) and VEGFR2 mRNAs and VEGF protein were increased in association with the ROP model and older developmental age and at time points when not only intravitreous neovascularization but also avascular retina were present in the ROP model and not in room air. Clinical Relevance Regulation of VEGF may have a role in the development of avascular retina and intravitreous neovascularization in some forms of severe ROP.
Budd
Steven J
SJ
Department of Ophthalmology, University of North Carolina, Chapel Hill, USA.
Thompson
Hilary
H
Hartnett
M Elizabeth
ME
D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007231:Infant, Newborn; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000235:genetics* / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen