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

J Cell Mol Med. 2017 May;21(5):968-974. doi: 10.1111/jcmm.13036. Epub 2016 Dec 20.


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.

Keywords: hyperglycaemia; melanocortin receptor agonists; oxidative stress; photoreceptors; primary retinal cell cultures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects
  • Glucose / toxicity*
  • Glutathione Peroxidase / metabolism
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Neuroprotection / drug effects*
  • Opsins / metabolism
  • Photoreceptor Cells, Vertebrate / enzymology*
  • Photoreceptor Cells, Vertebrate / pathology*
  • Primary Cell Culture
  • Receptors, Melanocortin / agonists*
  • Receptors, Melanocortin / metabolism
  • Staining and Labeling
  • Superoxide Dismutase / metabolism


  • Antioxidants
  • Opsins
  • Receptors, Melanocortin
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glucose