title: Melanocortin receptor agonists MCR1-5protect photoreceptors from high-glucose damage and restore antioxidant enzymes in primary retinal cell culture.
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.
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, Second University of Naples, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Maisto
authors.affiliation: Multidisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gesualdo
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, Second University of Naples, Naples, Italy.
authors.forename: Maria Consiglia
authors.initials: MC
authors.lastname: Trotta
authors.affiliation: Pharmacy Department, University of Naples Federico II, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.affiliation: Multidisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Testa
authors.affiliation: Multidisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Jorge Miquel
authors.initials: JM
authors.lastname: Barcia
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, Second University of Naples, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: D'Amico
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, Second University of Naples, Naples, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Di Filippo
authors.affiliation: Multidisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy.
authors.forename: Settimio
authors.initials: S
authors.lastname: Rossi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D000066829:Neuroprotection / Q000187:drug effects*; D055355:Opsins / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology* / Q000473:pathology*; D061251:Primary Cell Culture; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000378:metabolism; D013194:Staining and Labeling; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D055355:Opsins; D044101:Receptors, Melanocortin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005947:Glucose
keywords: hyperglycaemia; melanocortin receptor agonists; oxidative stress; photoreceptors; primary retinal cell cultures