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Background: X-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of RS1-associated retinal degeneration is not fully understood. Besides, animal models of XLRS have limitations in the study of XLRS. Here, we used human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) to investigate the disease mechanisms and potential treatments for XLRS., Methods: hiPSCs reprogrammed from peripheral blood mononuclear cells of two RS1 mutant (E72K) XLRS patients were differentiated into ROs. Subsequently, we explored whether RS1 mutation could affect RO development and explore the effectiveness of RS1 gene augmentation therapy., Results: ROs derived from RS1 (E72K) mutation hiPSCs exhibited a developmental delay in the photoreceptor, retinoschisin (RS1) deficiency, and altered spontaneous activity compared with control ROs. Furthermore, the delays in development were associated with decreased expression of rod-specific precursor markers (NRL) and photoreceptor-specific markers (RCVRN). Adeno-associated virus (AAV)-mediated gene augmentation with RS1 at the photoreceptor immature stage rescued the rod photoreceptor developmental delay in ROs with the RS1 (E72K) mutation., Conclusions: The RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy., (© 2024. The Author(s).)

X-linked retinoschisis (XLRS) is one of the most common retinal genetic diseases with progressive visual impairment in childhood affecting males. It is manifested with macular and/or peripheral schisis in neural retinas with no effective treatment. Previously, we successfully generated a human-induced pluripotent stem cell (iPSC) line from an XLRS patient carrying the hemizygous RS1 c. 304C > T (p.R102W) mutation. Here, we corrected the c.304C > T mutation in the RS1 gene using CRISPR/Cas9 technology to generate an isogenic control. This cell line is valuable for the study of XLRS., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

X-linked retinoschisis (XLRS) is a one of most common retinal genetic diseases of juvenile progressive vitreoretinal degeneration in males, which caused by the mutation of RS1 gene. In this study, an induced pluripotent stem cell (iPSC) line was generated from human peripheral blood mononuclear cells (PBMC) of a 13-year-old male patient with X-linked juvenile retinoschisis carrying a novel mutation in RS1 gene. The iPSCs exhibited iPSC morphology, expression of the pluripotency markers and in vitro differentiation potential, and the CSUASOi005-A iPSC line retained the original mutation (c.527T > A) of RS1 with a normal karyotype., 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 © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

X-linked juvenile retinoschisis (XLRS) is one of the most severely affected genetic causes of irreversible retinal degeneration diseases in young males, especially school-age boys. Here, we generated induced pluripotent stem cells (iPSCs) from a Chinese 11-year-old male with clinically diagnosed XLRS. Urine sample was collected with appropriate cooperation, then isolated cells were expanded for subsequent reprogramming procedure using integration-free Sendai virus. The newly derived CSUASOi001-A iPS cell line harboring the c.304C > T mutation in the RS1 gene (p.R102W) provides a useful resource to investigate pathogenic mechanisms in XLRS., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)