# RNA Sequencing and Targeted Knockdown Reveal miR-142a-5p as a Driver of Retinal Degeneration in rd1 Mice

## TL;DR

This study identifies miR-142a-5p as a driver of retinal degeneration in a mouse model of retinitis pigmentosa, suggesting it could be a target for new treatments.

## Contribution

The study reveals miR-142a-5p as a novel therapeutic target for retinal degenerative diseases.

## Key findings

- RNA sequencing identified 40 upregulated and 27 downregulated miRNAs in rd1 retinas.
- Knockdown of miR-142a-5p slowed retinal degeneration and preserved photoreceptor cells in rd1 mice.

## Abstract

Inherited eye diseases can cause the light-sensing cells to break down, leading to permanent blindness; there are very few treatments available. Our research focused on understanding the role of microRNAs, a kind of small RNA, which act as switches that can turn the expression of certain genes off inside cells. Using a mouse model of an inherited eye disease called retinitis pigmentosa, we discovered that the amounts of several of these microRNAs can either increase or decrease. One in particular, named miR-142, significantly increased in amount during disease progression. When we used a special tool to lower the amount of miR-142 in the eyes of these mice, we saw that the disease progressed more slowly; the mice retained more of their light-sensing cells and had better vision. This implies that miR-142 plays a key role in driving vision loss. Our study suggests that developing a drug to block miR-142 could be a promising new strategy for treating this type of blindness.

Retinitis pigmentosa (RP), an inherited retinal disorder, leads to progressive photoreceptor degeneration and irreversible blindness, with limited treatment options available. Emerging evidence implicates microRNAs (miRNAs) in the pathogenesis of retinal disease, yet understanding of their specific roles in RP remains incomplete. In this study, we employed high-throughput RNA sequencing to profile miRNA expression in a rd1 RP mouse model at postnatal day 14. Our analysis revealed 40 upregulated and 27 downregulated miRNAs in rd1 retinas compared to controls. Notably, miR-142a-5p, miR-223-3p, and miR-653-5p were significantly elevated, while miR-25-3p was downregulated. Given miR-142a-5p’s established roles in apoptosis and inflammation, we investigated its contribution to retinal degeneration. Knockdown of miR-142a-5p in rd1 mice improved retinal function and preserved outer nuclear layer thickness, suggesting a protective effect against photoreceptor loss. These findings highlight miR-142a-5p as a key regulator of RP progression and a promising therapeutic target for mitigating vision loss in retinal degenerative diseases.