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<https://discovery.ucl.ac.uk/id/eprint/10108968> <http://purl.org/ontology/bibo/abstract> "Current treatments for macular degeneration, such as gene therapy, pharmacological approaches and neuroprotective approaches require the present of the target cells, the photoreceptors, in order to achieve a successful outcome. This leaves several patients, where the retinal degeneration is too advanced, without any viable therapeutic alternative. Photoreceptor transplantation aims to replace the lost cells, providing a potential option for such cases. For photoreceptor replacement to succeed, transplanted photoreceptors must mature and establish synaptic connection with the host retina. The remodeling of the host retina must be considered, as its interneurons and synaptic circuits rearrange following photoreceptor degeneration. Additionally, an ethical and renewable source is required. Studies have shown that mouse and human embryonic stem cells (ESC) can be differentiated to photoreceptor and transplanted into models of retinal dystrophy. However, no unambiguous evidence of synaptic connectivity and rescue of vision have been achieved. Here a detailed characterization of the remodeling events following photoreceptor lost in Aipl1-/- animals is described. Aipl1-/- were chosen due to the severe and fast emerging phenotype. As expected, typical features of remodeling were identified in these retinas and potential morphological elements were selected for analysis, following transplantation. The transplantation conditions, specifically the number of transplanted cells, were optimized using mouse ESC-derived photoreceptors. Here was no evident cell maturation or integration in the host’s synaptic circuit, following transplantation. Interestingly, when transplanting human (h) ESC-derived cones indication of such events was seen. To increase the period post-transplantation Aipl1-/- and Rd1, another well-established model of end-stage retinal degeneration, mice were crossed with immuno-compromised animals. Twelve weeks following transplantation into immuno-compromised Rd1 mice, hESC-derived cones matured and established functional synapses with the host retina, achieving rescue of vision. Alternative explanations for the rescue seen can be excluded due to the use non-functional human induced pluripotent (hiPS)-derived cones as a sham control."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10108968> <http://purl.org/dc/terms/date> "2020-09-28" .
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