Photoreceptor preservation by FAAH inhibition in a murine model of retinitis pigmentosa.

Authors

Camila Feitosa Magalhães, Rafael de Freitas Azevedo-Repossi, Luana de Almeida-Pereira, Millena Costa Crisóstomo, Mariana Rodrigues Pereira, Karin da Costa Calaza, Hilda Petrs-Silva, Lucianne Fragel-Madeira

Published in

Molecular neurobiology. Volume 63. Issue 1. Jul 10, 2026. Epub Jul 10, 2026.

Abstract

Retinitis pigmentosa is a hereditary neurodegenerative disease characterized by gradual photoreceptor loss, often leading to blindness. The murine model Pde6b^rd10/rd10 (rd10) reproduces key features of retinitis pigmentosa (RP) and is widely used to evaluate therapeutic strategies. Anandamide is an endocannabinoid ligand degraded by fatty acid amide hydrolase (FAAH), whose levels have been shown to be increased in retinopathies. In this study, endocannabinoid signaling was pharmacologically augmented in rd10 mice to prolong photoreceptor survival. FAAH is present both in rd10 and C57Bl/6 retinas, with no differences in expression by qPCR or immunofluorescence analysis. To increase levels of endocannabinoid ligands URB597 (FAAH inhibitor), was administered daily by intraperitoneal injection (0.3 mg/kg), from P13 to P18 or P24. At P19, URB597 increased peripheral photoreceptor cell number by 35% and ONL thickness by 27%, with no effect in the central retina. At P25, peripheral photoreceptor number increased by 28%, although ONL thickness was unchanged. FAAH inhibition reduced TUNEL-positive cells in the peripheral retina by 50% and 53% at P19 and P25, respectively. No changes to reactive gliosis markers and microglia cells following FAAH inhibition were observed by assessing GFAP fluorescence intensity and Iba-1⁺ cell counts either in central or peripheral retina in both ages studied. Treatment with URB597 led to a 30% reduction in reactive oxygen species content at P19. Together, these data indicate a neuroprotective role of the endocannabinoid system in the context of photoreceptor degeneration in retinitis pigmentosa.

PMID:
42429887
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.