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Retinal organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that mimic the retina's spatial and temporal differentiation, making them useful as in vitro retinal development models. Retinal organoids can be assembled with brain organoids, the 3D self-assembled aggregates derived from hPSCs containing different cell types and cytoarchitectures that resemble the human embryonic brain. Recent studies have shown the development of optic cups in brain organoids. The cellular components of a developing optic vesicle-containing organoids include primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. The importance of retinal organoids in ocular diseases such as age-related macular degeneration, Stargardt disease, retinitis pigmentosa, and diabetic retinopathy are described in this review. This review highlights current developments in retinal organoid techniques, and their applications in ocular conditions such as disease modeling, gene therapy, drug screening and development. In addition, recent advancements in utilizing extracellular vesicles secreted by retinal organoids for ocular disease treatments are summarized.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653705 | PMC |
http://dx.doi.org/10.3390/cells11213429 | DOI Listing |
BMC Mol Cell Biol
September 2025
School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
Retinitis pigmentosa (RP) affects around 1 in 4000 individuals and represents approximately 25% of cases of vision loss in adults, through death of retinal rod and cone photoreceptor cells. It remains a largely untreatable disease, and research is needed to identify potential targets for therapy. Mutations in 94 different genes have been identified as causing RP, including AGBL5 which encodes the main deglutamylase that regulates and maintains functional levels of cilia tubulin glutamylation, which is essential to initiate ciliogenesis, maintain cilia stability and motility.
View Article and Find Full Text PDFRetinal organoids (ROs) represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but whether host cone bipolar cells (BCs) in the primate macula can rewire with transplanted photoreceptors remains unresolved. Here, we transplanted genome-edited human retinal organoids lacking ON-BCs ( ROs) into a non-human primate macular degeneration model. Remarkably, host rod and cone BCs extended dendrites toward grafted photoreceptors, forming functional synapses confirmed by immunohistochemistry, ultrastructural imaging, and focal macular electroretinography.
View Article and Find Full Text PDFAdv Mater
August 2025
Department of Medical Research, Taipei Veterans General Hospital, Taipei, 112201, Taiwan.
Gene therapy offers a promising treatment for Leber's hereditary optic neuropathy (LHON), a disease of retinal ganglion cell (RGC) degeneration with severe vision loss caused by mitochondria-NADH dehydrogenase 4 (MT-ND4) mutations. However, optimizing mitochondria-targeted gene delivery to promote RGC regeneration and visual-photoreception recovery remains challenging in LHON. Here, mitochondria-targeted wireless charging gold nanoparticles (WCGs), doubling as a wireless charging-mediated gene-delivery platform and electric stimulus-restored phototransduction, are developed for LHON treatment.
View Article and Find Full Text PDFGenes Dis
November 2025
Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
Age-related macular degeneration (AMD) poses a significant threat to the vision of the elderly population globally. Unfortunately, there is no effective treatment available for dry AMD. In this study, we utilized human retinal organoids (ROs) stimulated with sodium iodate to establish a model for dry AMD.
View Article and Find Full Text PDFBMC Res Notes
August 2025
Department of Anatomy and Embryology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Objective: The developing mammalian retina initially contains undifferentiated cells, providing a model for investigating the mechanisms of differentiation. Notch signaling, mediated by four Notch receptors (Notch 1-4) in mammals, has been studied in the differentiation of neural progenitor cells. Among the four Notch receptors, the frequency, rather than the peak level, of Notch1-mediated signaling has been suggested to promote the activation of neural progenitor cells.
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