Retinal stem cells (RSCs) are rare pigmented cells found in the pigmented ciliary layer of the mammalian retina. Studies show that RSCs can replicate to maintain the stem cell pool and produce retinal progenitors that differentiate into all retinal cell types. We classified RSCs based on their level and distribution of pigment into heavily pigmented (HP), lightly pigmented (LP), and centrally pigmented (CP) spheres. We report that CP spheres are capable of generating large cobblestone lawns of retinal pigment epithelial (RPE) cells. The other clonal sphere types (HP and LP) primarily produce cells with neural morphology and fewer RPE cells. The RSCs are homogeneous, but their downstream progenitors are different. We found that CP spheres contain highly proliferative populations of early RPE progenitors that respond to proliferative signals from the surrounding non-pigmented cells. HP and LP spheres contain late RPE progenitors which are not affected by proliferative signals.
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http://dx.doi.org/10.1016/j.isci.2021.102574 | DOI Listing |
The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ∼30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.
View Article and Find Full Text PDFClin Neurol Neurosurg
January 2025
Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Catholic University Leuven, Leuven, Belgium. Electronic address:
Objective: Surgeons routinely check the pupils to assess, in part, the brain stem function and the neural integrity of the visual system. Where a relative afferent pupillary defect is difficult to notice during surgery, an efferent pupillary defect or mydriasis is clearly recognizable. Visual loss in orbital surgery is attributed to compromised perfusion of the optic nerve, retina, or choroid, but an association with mydriasis is generally not assumed.
View Article and Find Full Text PDFStem Cell Res
January 2025
UCL Institute of Ophthalmology, London, UK; The Francis Crick Institute, London, UK; Moorfields Eye Hospital NHS Foundation Trust, London, UK. Electronic address:
A human induced pluripotent stem cell (hiPSC) line (UCLi025-A) was generated from dermal fibroblast cells from a 42-year-old female donor with polyneuropathy, hearing loss, retinitis pigmentosa and early-onset cataract (PHARC) syndrome carrying a homozygous nonsense variant in ABHD12 c.193C>T, p.(Arg65*).
View Article and Find Full Text PDFStem Cell Reports
January 2025
Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan; Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan. Electronic address:
We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1 ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biological Structure, University of Washington, Seattle, WA 98125.
Retinal diseases often lead to degeneration of specific retinal cell types with currently limited therapeutic options to replace the lost neurons. Previous studies have reported that overexpression of or combinations of proneural factors in Müller glia (MG) induce regeneration of functional neurons in the adult mouse retina. Recently, we applied the same strategy in dissociated cultures of fetal human MG and although we stimulated neurogenesis from MG, our effect in 2D cultures was modest and our analysis of newborn neurons was limited.
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