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

• Published in: Journal of cellular and molecular medicine Vol. 21; no. 5; pp. 968 - 974
• Main Authors: Maisto, Rosa, Gesualdo, Carlo, Trotta, Maria Consiglia, Grieco, Paolo, Testa, Francesco, Simonelli, Francesca, Barcia, Jorge Miquel, D'Amico, Michele, Di Filippo, Clara, Rossi, Settimio
• Format: Journal Article
• Language: English
• Published: 01.05.2017
• Subjects: hyperglycaemia; melanocortin receptor agonists; oxidative stress; photoreceptors; primary retinal cell cultures
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13036

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.