Related Experiment Video
Updated: Jul 1, 2025
Generation of Retinal Organoids from Healthy and Retinal Disease-Specific Human-Induced Pluripotent Stem Cells
Published on: December 9, 2022
Modeling autosomal dominant retinitis pigmentosa by using patient-specific retinal organoids with a class-3 RHO
Xiao Lin1, Zhuo-Lin Liu1, Xiao Zhang1
1Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Abstract:
Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP) causes progressive vision loss and is potentially incurable, accounting for 25% of adRP cases. Studies on RHO-adRP mechanism were at large based on the biochemical and cellular properties, especially class-3. Nonetheless, the absence of an appropriate model for class-3 RHO-adRP has impeded comprehensive exploration. Here, induced pluripotent stem cells (iPSCs) were generated from a healthy control and two sibling RP patients with the same point mutation, c.403C>T (p.R135W). The first three-dimensional (3D) retinal organoid model of a class-3 RHO point mutation from patient-derived iPSCs was generated. Significant defects were observed in rod photoreceptors in terms of localization, morphology, transcriptional profiling and single cell resolution, to better understand the human disease resulting from RHO mutations from a developmental perspective. This first human model of class-3 RHO-adRP provides a representation of patient's retina in vitro and displays features of RHO-adRP retinal organoids relevant for therapeutic development.
