The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity.
OBJECTIVE
Acidosis-induced retinopathy (AIR) in the neonatal rat provides an alternative model for retinopathy of prematurity (ROP). We studied the relationship of vascular endothelial growth factor (VEGF) retinal mRNA and insulin-like growth factor-1 (IGF-1) retinal mRNA expression with the emergence of neovascularization (NV) in AIR.


METHODS
Two hundred seventy-five newborn Sprague-Dawley rats were raised in 11 expanded litters of 25. Using our established AIR model, acidosis was induced by twice-daily gavage with NH4Cl from day 2 to day 8 of life (n=175). Rats were sacrificed at days 5, 8, and 10. Nongavaged rats were used as age-matched controls (n=100). Retinae from left eyes were dissected, flatmounts were ADPase-stained, and the presence and severity of NV was scored in a masked manner. Individual right retinae were processed for analysis of retinal VEGF and IGF-1 mRNA using quantitative real-time reverse-transcriptase PCR (qRT-PCR).


RESULTS
Retinal VEGF mRNA was increased 1.4-fold at day 10 in AIR, when compared with age-matched controls (p=0.03). This correlated with maximal NV at day 10 in AIR. Retinal IGF-1 mRNA was decreased to 82% of its normal expression on day 8 (p=0.006), prior to maximal NV, before returning to normal expression at day 10, when compared with nonacidotic controls.


CONCLUSIONS
In AIR, preretinal neovascularization is associated with decreased retinal IGF-1 mRNA prior to maximal NV and increased retinal VEGF mRNA at the time of maximal NV. These growth factor changes in AIR are similar to those seen with hypercarbic oxygen-induced retinopathy. The retinal IGF-1 pathway may provide an alternative target for therapeutic intervention in abnormal retinal angiogenesis.
Leske
David A
DA
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Wu
Jianmin
J
Mookadam
Martina
M
Chen
Yi
Y
Fautsch
Michael P
MP
Holmes
Jonathan M
JM
Lanier
William L
WL
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism*; D000643:Ammonium Chloride / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000643:Ammonium Chloride; D007334:Insulin-Like Growth Factor I