Many forms of blindness result from the dysfunction or loss of retinal photoreceptors. Induced pluripotent stem cells (iPSCs) hold great potential for the modelling of these diseases or as potential therapeutic agents. However, to fulfill this promise, a remaining challenge is to induce human iPSC to recreate in vitro key structural and functional features of the native retina, in particular the presence of photoreceptors with outer-segment discs and light sensitivity. Here we report that hiPSC can, in a highly autonomous manner, recapitulate spatiotemporally each of the main steps of retinal development observed in vivo and form three-dimensional retinal cups that contain all major retinal cell types arranged in their proper layers. Moreover, the photoreceptors in our hiPSC-derived retinal tissue achieve advanced maturation, showing the beginning of outer-segment disc formation and photosensitivity. This success brings us one step closer to the anticipated use of hiPSC for disease modelling and open possibilities for future therapies.
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http://dx.doi.org/10.1038/ncomms5047 | DOI Listing |
NPJ 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 PDFBiomimetics (Basel)
December 2024
Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada.
Three-dimensional bioprinting (3DP) is transforming the field of regenerative medicine by enabling the precise fabrication of complex tissues, including the retina, a highly specialized and anatomically complex tissue. This review provides an overview of 3DP's principles, its multi-step process, and various bioprinting techniques, such as extrusion-, droplet-, and laser-based methods. Within the scope of biomimicry and biomimetics, emphasis is placed on how 3DP potentially enables the recreation of the retina's natural cellular environment, structural complexity, and biomechanical properties.
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Department of Ophthalmology and Visual Sciences, The University of British Columbia, 2550 Willow St. Room 375, Vancouver, BC, V5Z 3N9, Canada.
Alzheimer's Disease (AD) is a debilitating neurodegenerative disease that affects 47.5 million people worldwide. AD is characterised by the formation of plaques containing extracellular amyloid-β (Aβ) and neurofibrillary tangles composed of hyper-phosphorylated tau proteins (pTau).
View Article and Find Full Text PDFRetina
January 2025
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.
Purpose: To determine the impact of eye shape using three-dimensional magnetic resonance imaging on myopic maculopathy (MM) progression.
Methods: At baseline, 67 participants with high myopia were selected. Eye shape was classified into spheroidal, ellipsoidal, temporally distorted, nasally distorted, conical, and barrel-shape identified from three-dimensional magnetic resonance imaging.
World J Transplant
December 2024
Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy.
New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells. Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells. Thus, the disruption of photoreceptors takes place.
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