Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Disease Models, Animal
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Drug Administration Schedule
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Gene Expression Regulation / drug effects
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Humans
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Hyperoxia / blood
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Hyperoxia / complications*
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Hyperoxia / physiopathology
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Infant, Newborn
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Injections, Subcutaneous
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Insulin-Like Growth Factor I / administration & dosage
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Insulin-Like Growth Factor I / analogs & derivatives
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Insulin-Like Growth Factor I / pharmacology*
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Insulin-Like Growth Factor II / metabolism
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Neovascularization, Pathologic / blood
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / etiology
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / physiopathology
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Peptides / administration & dosage
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Peptides / pharmacology*
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Retinal Vessels / drug effects*
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Retinal Vessels / metabolism
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Retinal Vessels / physiopathology
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Retinopathy of Prematurity / blood
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Retinopathy of Prematurity / drug therapy*
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Retinopathy of Prematurity / etiology
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Retinopathy of Prematurity / genetics
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Retinopathy of Prematurity / physiopathology
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Time Factors
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Vascular Endothelial Growth Factor A / blood
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Vascular Endothelial Growth Factor Receptor-1 / blood
Substances
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Peptides
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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vascular endothelial growth factor A, rat
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Insulin-Like Growth Factor I
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Insulin-Like Growth Factor II
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Flt1 protein, rat
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Vascular Endothelial Growth Factor Receptor-1