advertisement
Abstract #106267 Published in IGR 23-3
Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy
Shinozaki Y; Leung A; Namekata K; Saitoh S; Nguyen HB; Takeda A; Danjo Y; Morizawa YM; Shigetomi E; Sano F; Yoshioka N; Takebayashi H; Ohno N; Segawa T; Miyake K; Kashiwagi K; Harada T; Ohnuma SI; Koizumi SScience advances 2022; 8: eabq1081
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.
Full article