Melanocortin receptor agonists MCR1-5 protect photoreceptors from high-glucose damage and restore antioxidant enzymes in primary retinal cell culture

黑皮质素受体激动剂 MCR1-5 保护光感受器免受高葡萄糖损伤并恢复原代视网膜细胞培养中的抗氧化酶

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作者:Rosa Maisto, Carlo Gesualdo, Maria Consiglia Trotta, Paolo Grieco, Francesco Testa, Francesca Simonelli, Jorge Miquel Barcia, Michele D'Amico, Clara Di Filippo, Settimio Rossi

Abstract

Retinal photoreceptors are particularly vulnerable to local high-glucose concentrations. Oxidative stress is a risk factor for diabetic retinopathy development. Melanocortin receptors represent a family of G-protein-coupled receptors classified in five subtypes and are expressed in retina. Our previous data indicate that subtypes 1 and 5 receptor agonists exert a protective role on experimental diabetic retinopathy. This study focuses on their role in primary retinal cell cultures in high-glucose concentrations. After eye enucleation from wild-type male C57BL/6 mice, retinal cells were isolated, plated in high-glucose concentration and treated with melanocortin receptors 1 and 5 agonists and antagonists. Immunocytochemical and biochemical analysis showed that treatment with melanocortin receptors 1 and 5 agonists reduced anti-inflammatory cytokines and chemokines and enhanced manganese superoxide dismutase and glutathione peroxidase levels, preserving photoreceptor integrity. According with these evidences, we propose a major role of melanocortin receptors 1 and 5 on primary retinal cell response against high glucose or oxidative insults.

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