September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Activation of melanocortin receptors Mc1 and Mc5 attenuates retinal damage in experimental diabetic retinopathy.
Author Affiliations & Notes
  • Luigi Di Perna
    Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy
  • Carlo Gesualdo
    Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy
  • Rosa Maisto
    Department of Experimental Medicine, Second University of Naples, Naples, Italy
  • Clara Di Filippo
    Department of Experimental Medicine, Second University of Naples, Naples, Italy
  • Mauro Perretti
    The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom
  • Francesco Testa
    Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy
  • Settimio Rossi
    Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy
  • Michele D'amico
    Department of Experimental Medicine, Second University of Naples, Naples, Italy
  • Francesca Simonelli
    Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Naples, Italy
  • Footnotes
    Commercial Relationships   Luigi Di Perna, None; Carlo Gesualdo, None; Rosa Maisto, None; Clara Di Filippo, None; Mauro Perretti, None; Francesco Testa, None; Settimio Rossi, None; Michele D'amico, None; Francesca Simonelli, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 99. doi:
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      Luigi Di Perna, Carlo Gesualdo, Rosa Maisto, Clara Di Filippo, Mauro Perretti, Francesco Testa, Settimio Rossi, Michele D'amico, Francesca Simonelli; Activation of melanocortin receptors Mc1 and Mc5 attenuates retinal damage in experimental diabetic retinopathy.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):99.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The study aimed at evaluating the role of melanocortin (MC) peptides in the prevention of diabetic retinopathy (DR) and at characterizing the MC receptor subtype in an animal model of streptozotocin (STZ)-induced diabetes.

Methods : STZ-diabetes mice were randomized into the following experimental groups (n=10 animals per group) according to intravitreal injection (IVI): 1) Physiological saline; 2) MC1 receptor agonist 3) mixed MC3-MC4 receptor agonist 4) MC1 receptor antagonist 5) MC5 agonist 6) MC3-MC4 receptor antagonist 7) MC5 receptor antagonist. IVI were performed into the right eye every 4 weeks from the development of diabetes. Moreover, a group of non diabetic mice was used as healthy control. Fluorescein angiography (FAG) was conducted at week 8, 12 and 16.

Results : In the group 1, FAG showed the first changes of RD, i.e., retinal vessel with increased vascular tortuosity, irregular caliber and microvascular changes, at week 12 and their worsening at week 16. In the group 2 (MC1 receptor agonist) and group 5 (MC5 receptor agonist), FAG showed regular course and caliber of retinal vessels without microvascular changes or vessel leakage, differently from the group 1.
In group 4 and 7 (MC1 and MC5 selective antagonist, respectively), the retinal injury worsened with changes already evident after 8 weeks post-induction of diabetes, earlier than group 1; in particular, venous loop and an extensive retinal vessel leakage with progressive dye diffusion at 16 weeks post induction, a hyper-fluorescent areas were observed after treatment. In group 3 and 6 (MC3-MC4 agonist or the antagonist) no changes of the microvascular bed into the retina were observed.

Conclusions : Our findings suggested that stimulation of the MC system in the animal model through the local activation of MC1 and MC5 may reduce the retinal damage caused by diabetes. This may be the start of a melanocortin-based therapy for DR, especially when considering that several natural and synthetic melanocortin receptor agonists are under clinical experimentation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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