Inhibition of MicroRNA 6937 Delays Photoreceptor and Vision Loss in a Mouse Model of Retinitis Pigmentosa
Open Access
- 24 September 2020
- journal article
- research article
- Published by MDPI AG in Pharmaceutics
- Vol. 12 (10), 913
- https://doi.org/10.3390/pharmaceutics12100913
Abstract
Inherited retinal dystrophies (IRDs) are a group of rare retinal conditions, including retinitis pigmentosa (RP), caused by monogenic mutations in 1 out of more than 250 genes. Despite recent advancements in gene therapy, there is still a lack of an effective treatment for this group of retinal conditions. MicroRNAs (miRNAs) are a class of highly conserved small non-coding RNAs that inhibit gene expression. Control of miRNAs-mediated protein expression has been described as a widely used mechanism for post-transcriptional regulation in many physiological and pathological processes in different organs, including the retina. Our main purpose was to test the hypothesis that modulation of a group of miRNAs can protect photoreceptor cells from death in the rd10 mouse model of retinitis pigmentosa. For this, we incorporated modulators of three miRNAs in adeno-associated viruses (AAVs), which were administered through sub-retinal injections. The results obtained indicate that inhibition of the miR-6937-5p slows down the visual deterioration of rd10 mice, reflected by an increased electroretinogram (ERG) wave response under scotopic conditions and significant preservation of the outer nuclear layer thickness. This work contributes to broadening our knowledge on the molecular mechanisms underlying retinitis pigmentosa and supports the development of novel therapeutic approaches for RP based on miRNA modulation.Funding Information
- Instituto de Salud Carlos III (CP10/00572, CPII16/0012; PI13/02621, PI18/00507, PI17/01413 and RD16/0008/0027)
- Eusko Jaurlaritza (2018111062, MTVD19/BD/006, MTVD20/BD/002, SAIO11-PE11BN002, SAIO12-PC12BN001, DEPLC13/002)
This publication has 53 references indexed in Scilit:
- Characterization of a new murine retinal cell line (MU-PH1) with glial, progenitor and photoreceptor characteristicsExperimental Eye Research, 2013
- Changes in Apoptotic Mechanisms Following Penetrating Ballistic-Like Brain InjuryJournal of Molecular Neuroscience, 2012
- Elevated miR-155 Promotes Inflammation in Cystic Fibrosis by Driving Hyperexpression of Interleukin-8Online Journal of Public Health Informatics, 2011
- Angiopoietin-1/Tie2 signaling pathway inhibits lipopolysaccharide-induced activation of RAW264.7 macrophage cellsBiochemical and Biophysical Research Communications, 2010
- A common microRNA signature in mouse models of retinal degenerationExperimental Eye Research, 2008
- Toward MicroRNA–Based Therapeutics for Heart DiseaseCirculation Research, 2008
- Attenuation of Vision Loss and Delay in Apoptosis of Photoreceptors Induced by Proinsulin in a Mouse Model of Retinitis PigmentosaInvestigative Ophthalmology & Visual Science, 2008
- Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosaGenome Biology, 2007
- ?-amyloid peptide binding protein does not couple to G protein in a heterologousXenopus expression systemJournal of Neuroscience Research, 2003
- μ-Amyloid Peptide-induced Apoptosis Regulated by a Novel Protein Containing a G Protein Activation ModuleJournal of Biological Chemistry, 2001