Efeitos biomoleculares do JB-1 (um peptídeo análogo do IGF-1) em um modelo experimental de retinopatia induzida por oxigênio em ratos / Biomolecular effects of jb-1 (an igf-1 peptide analog) in a Rat model of oxygen-induced retinopathy

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

08/12/2011

RESUMO

INTRODUCTION: Low serum insulin growth factor (IGF-1) levels at birth is a risk factor for the development of retinopathy of prematurity in extremely low birth weight infants. This may be due to its role as a permissive factor for vascular endothelial growth factor (VEGF) function in normal and pathologic vascular development. OBJECTIVE: To test the hypothesis that JB-1 (an IGF-1 analog that potently inhibits the autophosphorylation of the IGF-1 receptor by IGF-1) administration during hyperoxia prevents oxygen induced retinopathy in our rat model. MATERIAL AND METHODS: Neonatal rats were exposed to 50% oxygen with brief, clustered, hypoxic (12% oxygen) episodes from birth to day 14. The pups were treated with subcutaneus injections of 1) JB-1 (1g/d) on the first, second, and third day (JB-1x3) 2) JB1 (1g/d) on alternate days from first to day 13 (JB- 1x7); or equivalent volume of saline. Control littermates were raised in room air with all conditions identical except for inspired oxygen. Groups were analyzed after hyperoxia/hypoxia cycling on day 14 or allowed to recover in room air until the 21st day. Systemic and ocular VEGF, soluble VEGFR-1, and IGF-1; retinal vasculature and gene profile of retinal angiogenesis were assessed. RESULTS: JB-1x3 treatment resulted in successful suppression of oxygeninduced retinopathy with no adverse effect on anthropometric growth, which was associated with increased sVEGFR-1 compared to JB-1x7. In contrast, intermittent and long exposure to JB-1 (JB-1x7) during the hyperoxia/hypoxia cycling period resulted in decreased body weight and higher ocular IGF-1 and VEGF levels as well as vascular tortuosity and retinal neovascularization compared with saline treated retinas. CONCLUSION: Systemic treatment with JB-1 during hyperoxia results in successful prevention of oxygen-induced retinopathy with little adverse effects on anthropometric growth. Further confirmatory studies are needed to determine whether systemic JB-1 should be used in extremely low birth weight infants to prevent retinopathy of prematurity

ASSUNTO(S)

fator de crescimento insulin-like 1 hiperóxia hyperoxia infant newborn oxygen ratos sprague-dawley rats recém-nascido retinopathy of prematurity retinopatia da prematuridade sprague-dawley insulin-like growth factor 1 oxigênio

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