Dominant <i>RDH12</i>-retinitis pigmentosa impairs photoreceptor development and implicates cone involvement in retinal organoids.

ABSTRACT:

Introduction

Retinal dehydrogenase 12 (RDH12) is a photoreceptor NADPH-dependent retinal reductase enzyme, converting all-trans-retinal to all-trans-retinol. Heterozygous variants in RDH12 cause a rare autosomal dominant (AD) retinitis pigmentosa.

Methods

As no disease models exist, we generated human induced pluripotent stem cell-derived retinal organoids (RO) from an RDH12-AD patient (with pathogenic variant c.759del, p.Phe254Leufs*24) alongside a healthy, unaffected control.

Results

RDH12-AD RO exhibited correct localization of RDH12 to the photoreceptor inner segments up to week 44; however, transmission electron microscopy at week 37 showed that photoreceptors were less abundant and shorter in length. Visual cone function

SUBMITTER: Mejecase C 

PROVIDER: S-EPMC12069300 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature