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.
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http://dx.doi.org/10.1038/s12276-021-00588-w | DOI Listing |
Biomolecules
January 2025
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.
View Article and Find Full Text PDFExp Eye Res
January 2025
Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215000, China; Key Laboratory of Geriatric Diseases and Immunology, Ministry of Education, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Suzhou 215123, China. Electronic address:
Due to its unique physiological structure and functions, the eye has received considerable attention in the field of Adeno-associated virus (AAV) gene therapy. Inherited retinal degenerative diseases, which arise from pathogenic mutations in mRNA transcripts expressed in the eye's photoreceptor cells or retinal pigment epithelium (RPE), are the most common cause of vision loss. However, current retinal gene therapy mostly involves subretinal injection of therapeutic genes, which treats a limited area, entails retinal detachment, and requires sophisticated techniques.
View Article and Find Full Text PDFPhytomedicine
January 2025
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; Department of Ophthalmology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China. Electronic address:
Background: Resistance to senescence in retinal pigment epithelial (RPE) cells can delay the progression of age-related macular degeneration (AMD). However, the mechanisms underlying RPE cell senescence remain inadequately understood, and effective therapeutic strategies are lacking. While astragaloside IV (Ast) has demonstrated anti-aging properties, its specific effects on RPE cell senescence and potential mechanisms are not yet fully clarified.
View Article and Find Full Text PDFAmyloid β (Aβ) has emerged as a pathophysiological driver in age-related macular degeneration (AMD), emphasizing its significance in the aetiology of this prevalent sight-threatening condition. The multifaceted nature of AMD pathophysiology, presumably involving diverse retinal cascades, corresponds with the complexity of Aβ-induced retinopathy. Therefore, targeting a broad array of pathogenic processes holds promise for therapeutic intervention in AMD-associated retinal pathology.
View Article and Find Full Text PDFSci Adv
January 2025
Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.
Reward prediction errors (RPEs) quantify the difference between expected and actual rewards, serving to refine future actions. Although reinforcement learning (RL) provides ample theoretical evidence suggesting that the long-term accumulation of these error signals improves learning efficiency, it remains unclear whether the brain uses similar mechanisms. To explore this, we constructed RL-based theoretical models and used multiregional two-photon calcium imaging in the mouse dorsal cortex.
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