Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study.
diabetic retinopathy
fingolimod
melanocortin receptor 1
melanocortin receptor 5
sphingosine 1-phosphate receptor
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
01
06
2021
accepted:
20
08
2021
entrez:
4
10
2021
pubmed:
5
10
2021
medline:
5
10
2021
Statut:
epublish
Résumé
This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (
Identifiants
pubmed: 34603029
doi: 10.3389/fphar.2021.718902
pii: 718902
pmc: PMC8484636
doi:
Types de publication
Journal Article
Langues
eng
Pagination
718902Informations de copyright
Copyright © 2021 Gesualdo, Balta, Platania, Trotta, Herman, Gharbia, Rosu, Petrillo, Giunta, Della Corte, Grieco, Bellavita, Simonelli, D’Amico, Hermenean, Rossi and Bucolo.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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