Endoplasmic reticulum stress and rhodopsin accumulation in an organoid model of Retinitis Pigmentosa carrying a RHO pathogenic variant.

ABSTRACT:

Background

Retinitis Pigmentosa (RP) is the most prevalent inherited retinal dystrophy, with more than 120 causative genes. Among them, RHO was the first photoreceptor gene described to harbor mutations responsible for RP. RHO pathogenic variants usually induce a dominant negative effect in which the accumulation of misfolded rhodopsin protein leads to ER stress, autophagy and lastly rod photoreceptor death.

Methods

We differentiated photoreceptor precursors and retinal organoids from an iPSC line of a patient carrying the Pro215Leu mutation in RHO gene. Both cell models were analyzed to determine their maturation, the expression and localization of RHO mRNA and the rhodopsin protein and the activation of autophagy or ER pathways.

Results

The Pro215Leu mutation causes

SUBMITTER: Navines-Ferrer A 

PROVIDER: S-EPMC11827366 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature