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Mediators of Inflammation
Volume 2016, Article ID 7368389, 13 pages
Research Article

Activation of Melanocortin Receptors MC1 and MC5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy

1Multidisciplinary Department of Medical-Surgical and Dental Specialties, Second University of Naples, 80138 Naples, Italy
2Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
3Department of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, Italy
4The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK
5Faculty of Science and Technology, Department of Life Sciences, University of Westminster, London W1W 6UW, UK
6Department of Translational Medicine, University of Naples Federico II, 80131 Naples, Italy
7Pharmacy Department, University of Naples Federico II, 80131 Naples, Italy

Received 2 October 2015; Revised 1 December 2015; Accepted 15 December 2015

Academic Editor: Elaine Hatanaka

Copyright © 2016 S. Rossi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12–16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors, Mc1r and Mc5r. The intravitreal injection (5 μL) of the selective MC1 small molecule agonist BMS-470539 (33 μmol) and the MC5 peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1α, IL-1β, IL-6, MIP-1α, MIP-2α, MIP-3α, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5 and MC1 antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4 agonist/antagonists resulted to be inactive with respect to all parameters under assessment.