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Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy

Shinozaki, Youichi; Leung, Alex; Namekata, Kazuhiko; Saitoh, Sei; Nguyen, Huy Bang; Takeda, Akiko; Danjo, Yosuke; ... Koizumi, Schuichi; + view all (2022) Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy. Science Advances , 8 (44) , Article eabq1081. 10.1126/sciadv.abq1081. Green open access

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Abstract

Astrocyte abnormalities have received great attention for their association with various diseases in the brain but not so much in the eye. Recent independent genome-wide association studies of glaucoma, optic neuropathy characterized by retinal ganglion cell (RGC) degeneration, and vision loss found that single-nucleotide polymorphisms near the ABCA1 locus were common risk factors. Here, we show that Abca1 loss in retinal astrocytes causes glaucoma-like optic neuropathy in aged mice. ABCA1 was highly expressed in retinal astrocytes in mice. Thus, we generated macroglia-specific Abca1-deficient mice (Glia-KO) and found that aged Glia-KO mice had RGC degeneration and ocular dysfunction without affected intraocular pressure, a conventional risk factor for glaucoma. Single-cell RNA sequencing revealed that Abca1 deficiency in aged Glia-KO mice caused astrocyte-triggered inflammation and increased the susceptibility of certain RGC clusters to excitotoxicity. Together, astrocytes play a pivotal role in eye diseases, and loss of ABCA1 in astrocytes causes glaucoma-like neuropathy.

Type: Article
Title: Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/sciadv.abq1081
Publisher version: https://doi.org/10.1126/sciadv.abq1081
Language: English
Additional information: Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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
URI: https://discovery.ucl.ac.uk/id/eprint/10158965
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