| First Author | Shinozaki Y | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 44 | Pages | eabq1081 |
| PubMed ID | 36332025 | Mgi Jnum | J:331255 |
| Mgi Id | MGI:7386335 | Doi | 10.1126/sciadv.abq1081 |
| Citation | Shinozaki Y, et al. (2022) Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy. Sci Adv 8(44):eabq1081 |
| abstractText | 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. |
