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Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina

Martins, Raquel R; Zamzam, Mazen; Tracey-White, Dhani; Moosajee, Mariya; Thummel, Ryan; Henriques, Catarina M; MacDonald, Ryan B; (2022) Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina. Aging Cell , Article e13597. 10.1111/acel.13597. Green open access

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Abstract

Ageing is a significant risk factor for degeneration of the retina. Müller glia cells (MG) are key for neuronal regeneration, so harnessing the regenerative capacity of MG in the retina offers great promise for the treatment of age-associated blinding conditions. Yet, the impact of ageing on MG regenerative capacity is unclear. Here, we show that the zebrafish retina undergoes telomerase-independent, age-related neurodegeneration but that this is insufficient to stimulate MG proliferation and regeneration. Instead, age-related neurodegeneration is accompanied by MG morphological aberrations and loss of vision. Mechanistically, yes-associated protein (Yap), part of the Hippo signalling, has been shown to be critical for the regenerative response in the damaged retina, and we show that Yap expression levels decline with ageing. Despite this, morphologically and molecularly altered aged MG retain the capacity to regenerate neurons after acute light damage, therefore, highlighting key differences in the MG response to high-intensity acute damage versus chronic neuronal loss in the zebrafish retina.

Type: Article
Title: Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/acel.13597
Publisher version: https://doi.org/10.1111/acel.13597
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Müller glia, Zebrafish, ageing, degeneration, proliferation, regeneration, retina, telomerase
UCL classification: 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
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10145992
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