Abstract
Retinal degenerative disorders, including age-related macular degeneration and retinitis pigmentosa (RP), are characterized by the irreversible loss of photoreceptor cells and retinal pigment epithelial (RPE) cells; however, the long-term effect of implanting both human induced pluripotent stem cell (hiPSC)-derived RPE and photoreceptor for retinal regeneration has not yet been investigated. In this study, we evaluated the long-term effects of hiPSC-derived RPE and photoreceptor cell transplantation in Pde6b knockout rats to study RP; cells were injected into the subretinal space of the right eyes of rats before the appearance of signs of retinal degeneration at 2–3 weeks of age. Ten months after transplantation, we evaluated the cells using fundus photography, optical coherence tomography, and histological evaluation, and no abnormal cell proliferation was observed. A relatively large number of transplanted cells persisted during the first 4 months; subsequently, the number of these cells decreased gradually. Notably, immunohistochemical analysis revealed that the hiPSC-derived retinal cells showed characteristics of both RPE cells and photoreceptors of human origin after transplantation. Functional analysis of vision by scotopic electroretinogram revealed significant preservation of vision after transplantation. Our study suggests that the transplantation of hiPSC-derived retinal cells, including RPE cells and photoreceptors, has a potential therapeutic effect against irreversible retinal degenerative diseases.
Highlights
The retina is neural tissue located in the posterior part of the eye and is an extension of the central nervous system (CNS), which has limited regenerative potential once damaged[1]
While published studies on the differentiation of human induced pluripotent stem cell (hiPSC) into retinal pigment epithelial (RPE) cells are available, there are no reports in which transplanted hiPSC-derived retinal cells simultaneously show the characteristics of photoreceptor cells and RPE cells[16]
The hiPSC-derived retinal cells used for transplantation in our study exhibited the characteristics of both photoreceptor cells and RPE cells
Summary
The retina is neural tissue located in the posterior part of the eye and is an extension of the central nervous system (CNS), which has limited regenerative potential once damaged[1]. The outer BRB is mainly composed of retinal pigment epithelial (RPE) cells, These disorders are commonly characterized by the irreversible loss of photoreceptor cells and RPE cells, and the only fundamental treatment for these retinal degenerative disorders is replacement of damaged or atrophied cells[10,11,12]. Regenerative treatments, such as stem cell transplantation, are emerging as attractive options for targeting retinal degeneration that was previously considered untreatable[13]. Due to its inherent nature, extensive genetic studies are ongoing, and more than 50 causal genes have
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