Cell transplantation is an active field of research to replace lost cells in retinal dystrophies to potentially restore visual function. We hypothesized that in-vitro differentiated retinal stem cells would integrate the appropriate retinal layer and differentiate into photoreceptors when transplanted during development. Here we show that retinal stem cells driven to the photoreceptor fate start to incorporate the retina and express photoreceptor markers but do not survive. Nevertheless surviving grafted cells express the glial marker glial fibrillary acidic protein and incorporate the ganglion cell layer as well as the inner plexiform layer. These results suggest that the maturation state of the photoreceptors is primordial to obtain robust incorporation and that a fine tuning of retinal stem cells differentiation should provide adequate cells for transplantation.
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http://dx.doi.org/10.1097/WNR.0b013e32815277c1 | DOI Listing |
Nat Commun
December 2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.
View Article and Find Full Text PDFNPJ Regen Med
December 2024
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.
As an emerging type of pluripotent stem cells, chemically induced pluripotent stem cells (CiPSCs) avoid the risks of genomic disintegration by exogenous DNAs from viruses or plasmids, providing a safer stem cell source. To verify CiPSCs' capacity to differentiate into retinal organoids (ROs), we induced CiPSCs from mouse embryonic fibroblasts by defined small-molecule compounds and successfully differentiated the CiPSCs into three-dimensional ROs, in which all major retinal cell types and retinal genes were in concordance with those in vivo. We transplanted retinal photoreceptors from ROs into the subretinal space of retinal degeneration mouse models and the cells could integrate into the host retina, establish synaptic connections, and significantly improve the visual functions of the murine models.
View Article and Find Full Text PDFMicrocirculation
January 2025
Eye Research Center, The Five Senses Health Institute, Moheb Kowsar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Purpose: To assess the colocalization of ellipsoid zone (EZ) disruption with nonperfusion in choriocapillaris (CC), retinal superficial capillary plexus (SCP), and deep capillary plexus (DCP) in diabetic patients using en face optical coherence tomography (OCT) and OCT angiography (OCTA).
Methods: Macular OCT and OCTA scans (3 × 3 mm) of 41 patients with diabetic retinopathy were obtained using an RTVue XR Avanti instrument. After correcting the shadow artifacts, EZ integrity was assessed in the en face OCT slab using the Gaussian mixture model clustering method compared with the corresponding EZ en face OCT of 11 age-matched normal patients.
Stem Cells Transl Med
December 2024
NEI/OSCTRS/OGVFB, Bethesda, MD, United States.
Retinal pigment epithelium (RPE) atrophy is a significant cause of human blindness worldwide, occurring in polygenic diseases such as age-related macular degeneration (AMD) and monogenic diseases such as Stargardt diseases (STGD1) and late-onset retinal degeneration (L-ORD). The patient-induced pluripotent stem cells (iPSCs)-derived RPE (iRPE) model exhibits many advantages in understanding the cellular basis of pathological mechanisms of RPE atrophy. The iRPE model is based on iPSC-derived functionally mature and polarized RPE cells that reproduce several features of native RPE cells, such as phagocytosis of photoreceptor outer segments (POS) and replenishment of visual pigment.
View Article and Find Full Text PDFExp Eye Res
December 2024
Departments of Biochemistry and Ophthalmology, University of Washington, Seattle, WA, USA. Electronic address:
Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE).
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