Astrocytic Dysfunction Induced by ABCA1 Deficiency Causes Optic Neuropathy

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Nov 4

PMID 36332025

Authors

Youichi Shinozaki

Alex Leung

Kazuhiko Namekata

Sei Saitoh

Huy Bang Nguyen

Akiko Takeda

Yosuke Danjo

Yosuke M Morizawa

Eiji Shigetomi

Fumikazu Sano

Nozomu Yoshioka

Hirohide Takebayashi

Nobuhiko Ohno

Takahiro Segawa

Kunio Miyake

Kenji Kashiwagi

Takayuki Harada

Shin-ichi Ohnuma

Schuichi Koizumi

Affiliations

Soon will be listed here.

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 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 -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 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.

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