Biomolecular effects of JB1 (an IGF-I peptide analog) in a rat model of oxygen-induced retinopathy.
Low-serum IGF-I levels at birth is a risk factor for the development of retinopathy of prematurity in extremely LBW infants. We tested the hypothesis that JB1 (an IGF-I analog) prevents oxygen-induced retinopathy in our rat model. Neonatal rats were exposed to 50% oxygen with brief, clustered, hypoxic (12%) episodes from birth to P14. The pups were treated with s.c. injections of 1) JB1 (1 μg/d) on P1, P2, and P3 (JB1x3); 2) JB1 (1 μg/d) on alternate days from P1 to P13 (JB1x7); or 3) equivalent volume saline. Control littermates were raised in room air (RA) with all conditions identical except for inspired O2. Groups were analyzed after hyperoxia/hypoxia (H/H) cycling at P14 or allowed to recover in RA until P21. Systemic and ocular VEGF, soluble VEGFR-1, and IGF-I; retinal vasculature; and gene profile of retinal angiogenesis were assessed. JB1x3 was more effective with associated increases in sVEGFR-1 and decreased retinal pathologies than JB1x7. We conclude that early short-term exposure to systemic JB1 treatment normalizes retinal abnormalities seen with H/H cycling, an effect that may involve sVEGFR-1.
Department of Pediatrics, University of California Irvine, Irvine, California 92868, USA.
Romy S
RS
Brock
Bisrat H
BH
Gebrekristos
Katherine M
KM
Kuniyoshi
Houchang D
HD
Modanlou
Mario Cicero
MC
Falcao
Kay D
KD
Beharry
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018496:Hyperoxia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D007231:Infant, Newborn; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D010455:Peptides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1