Ribeiro, J;
Procyk, CA;
West, EL;
O'Hara-Wright, M;
Martins, MF;
Khorasani, MM;
Hare, A;
... Ali, RR; + view all
(2021)
Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors.
Cell Reports
, 35
(3)
, Article 109022. 10.1016/j.celrep.2021.109022.
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Abstract
Age-related macular degeneration and other macular diseases result in the loss of light-sensing cone photoreceptors, causing irreversible sight impairment. Photoreceptor replacement may restore vision by transplanting healthy cells, which must form new synaptic connections with the recipient retina. Despite recent advances, convincing evidence of functional connectivity arising from transplanted human cone photoreceptors in advanced retinal degeneration is lacking. Here, we show restoration of visual function after transplantation of purified human pluripotent stem cell-derived cones into a mouse model of advanced degeneration. Transplanted human cones elaborate nascent outer segments and make putative synapses with recipient murine bipolar cells (BCs), which themselves undergo significant remodeling. Electrophysiological and behavioral assessments demonstrate restoration of surprisingly complex light-evoked retinal ganglion cell responses and improved light-evoked behaviors in treated animals. Stringent controls exclude alternative explanations, including material transfer and neuroprotection. These data provide crucial validation for photoreceptor replacement therapy and for the potential to rescue cone-mediated vision.
| Type: | Article |
|---|---|
| Title: | Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2021.109022 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2021.109022 |
| Language: | English |
| Additional information: | Copyright © 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | cell therapy, cone photoreceptor, degeneration, electrophysiology, macular degeneration, outer segment, rescue, retinal organoid, transplantation, visual function |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126666 |
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