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Retinitis pigmentosa (RP) is one of the most common inherited retinal diseases characterized by nyctalopia, progressive vision loss and visual field contraction. we previously generated an induced pluripotent stem cell line (CSUASOi004-A) from a RP patient with heterozygous PRPF6 c.2699 G>A (p.R900H) mutation. Here we corrected the PRPF6 c.2699 G>A mutation genetically using CRISPR/Cas9 technology to generate an isogenic control (CSUASOi004-A-1), which can provide a valuable resource in the research of the disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pre-mRNA processing factors (PRPFs) are vital components of the spliceosome and are involved in the physiological process necessary for pre-mRNA splicing to mature mRNA. As an important member, PRPF6 mutation resulting in autosomal dominant retinitis pigmentosa (adRP) is not common. Recently, we reported the establishment of an induced pluripotent stem cells (iPSCs; CSUASOi004-A) model by reprogramming the peripheral blood mononuclear cells of a PRPF6 -related adRP patient, which could recapitulate a consistent disease-specific genotype. In this study, a disease model of retinal pigment epithelial (RPE) cells was generated from the iPSCs of this patient to further investigate the underlying molecular and pathological mechanisms. The results showed the irregular morphology, disorganized apical microvilli and reduced expressions of RPE-specific genes in the patient's iPSC-derived RPE cells. In addition, RPE cells carrying the PRPF6 mutation displayed a decrease in the phagocytosis of fluorescein isothiocyanate-labeled photoreceptor outer segments and exhibited impaired cell polarity and barrier function. This study will benefit the understanding of PRPF6 -related RPE cells and future cell therapy.

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by the progressive photoreceptors and pigment epithelial cells dysfunction. Here, we report the human induced pluripotent stem cell line (iPSC) CSUASOi006-A, generated from urine-derived cells (UCs) of a 17-year-old male patient with clinically diagnosed RP carrying point mutation (c.C5792T) in the pre-mRNA processing factor 8 gene (PRPF8). The newly derived CSUASOi006-A cell line has the patient's same mutation (c.C5792T) and could provide useful resources for studying the pathogenic mechanism of PRPF8-related RP., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

We have established the patient-specific induced pluripotent stem (iPS) cell line CSUASOi004-A by using peripheral blood mononuclear cells (PBMCs) of a retinitis pigmentosa (RP) patient with a PRPF6 gene mutation (c.G2699A:p.R900H). CSUASOi004-A was established by a non-integrative method with four episomal plasmids containing the Yamanaka factors. The cell line with the specific point mutation had the typical features of normal iPS cells. For instance, the cells expressed pluripotency markers, generated all three germ layers and had a normal karyotype, and they can serve as a model for unravelling the pathogenic mechanisms underlying PRPF6-associated retinal degeneration., Competing Interests: Author disclosure statement There are no competing financial interests with respect to this study., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

We have established an induced pluripotent stem (iPS) cell line using urine-derived cells from a 27-year-old male patient with retinitis pigmentosa associated with point mutations in the USH2A gene. Feeder-free culture conditions and the integration-free CytoTune™-iPS 2.0 Sendai Reprogramming Kit were used., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Retinitis pigmentosa (RP) represents a group of inherited retinopathies with early-onset nyctalopia followed by progressive photoreceptor degeneration causing irreversible vision loss. Mutations in USH2A are the most common cause of non-syndromic RP. Here, we reprogrammed induced pluripotent stem cells (iPSCs) from a RP patient with a mutation in USH2A (c.8559-2A > G/c.9127_9129delTCC). Then, multilayer retinal organoids including neural retina (NR) and retinal pigment epithelium (RPE) were generated by three-step "induction-reversal culture." The early retinal organoids derived from the RP patient with the USH2A mutation exhibited significant defects in terms of morphology, immunofluorescence staining and transcriptional profiling. To the best of our knowledge, the pathogenic mutation (c.9127_9129delTCC) in USH2A has not been reported previously among RP patients. Notably, the expression of laminin in the USH2A mutation organoids was significantly lower than in the iPSCs derived from healthy, age- and sex-matched controls during the retinal organogenesis. We also observed that abnormal retinal neuroepithelium differentiation and polarization caused defective retinal progenitor cell development and retinal layer formation, disordered organization of NRs in the presence of the USH2A mutation. Furthermore, the USH2A mutation bearing RPE cells presented abnormal morphology, lacking pigmented foci and showing an apoptotic trend and reduced expression of specific makers, such as MITF, PEDF , and RPE65. In addition, the USH2A mutation organoids had lower expression of cilium-associated (especially CFAP43 , PIFO) and dopaminergic synapse-related genes (including DLGAP1 , GRIK1 , SLC17A7 , and SLC17A8), while there was higher expression of neuron apoptotic process-related genes (especially HIF1A , ADARB1 , and CASP3). This study may provide essential assistance in the molecular diagnosis and screening of RP. This work recapitulates the pathogenesis of USH2A using patient-specific organoids and demonstrated that alterations in USH2A function due to mutations may lead to cellular and molecular abnormalities. A model of USH2A mutation-associated 3D retinal developmental abnormalities. [ABSTRACT FROM AUTHOR]