期刊
SCIENCE ADVANCES
卷 8, 期 44, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abq1081
关键词
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资金
- Takeda Science Foundation
- Mitsubishi Foundation
- Japan Agency for Medical Research and Development [20gm1310008s0101]
- Japan Society for the Promotion of Science KAKENHI [JP16K18390, JP18K06481, JP20KK0366, JP20K07751, JP19KK0229, JP21H02819, JP21K18279, JP16H06280, JP16H04669, JP25117003, JP18H05121, JP19H04746, JP20H05902, JP20H05984, JP21H04786]
- JST Grant CREST [JPMJCR14G2]
- AMED-CREST [JP20gm131000]
- Moorfields Eye Charity [MEC1601A]
- University of Yamanashi
- Santen SenSyT studentship
- Cooperative Research Program of the Network Joint Research Center for Materials and Devices
Loss of ABCA1 in retinal astrocytes causes glaucoma-like optic neuropathy in aged mice, leading to retinal ganglion cell degeneration and ocular dysfunction.
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.
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