Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.

Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.
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DOI:
10.1186/s40478-022-01448-y
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发表时间:
2022-10-05
影响因子:
7.1
通讯作者:
--
中科院分区:
医学2区
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淀粉样蛋白β (a β)沉积在阿尔茨海默病(AD)眼视网膜中,可能为AD的诊断提供有用的生物标志物。本研究的重点是Aβ与大胶质细胞和小胶质细胞的关系,因为这些胶质细胞被假设在AD视网膜的内稳态和Aβ清除中起重要作用。与对照组相比,AD患者的Aβ负荷明显升高,特别是在中外周区域。与对照组相比,AD视网膜对胶质纤维酸性蛋白(GFAP)和谷氨酰胺合成酶(GS)的免疫反应性明显降低。对小胶质细胞标志物离子钙结合适配器分子-1 (IBA-1)的免疫反应表明,与对照视网膜相比,AD患者的小胶质细胞增生水平更高。在AD视网膜中,IBA-1免疫反应性更多地存在于中周视网膜中,其中含有更多的Aβ。GFAP很少与Aβ共定位,而IBA-1与Aβ共定位的对照层数多于AD供体视网膜。这些结果表明,突触和小胶质细胞的功能障碍可能是AD视网膜的关键特征。在线版本包含补充材料,可在10.1186/s40478-022-01448-y获得。
Amyloid beta (Aβ) deposits in the retina of the Alzheimer’s disease (AD) eye may provide a useful diagnostic biomarker for AD. This study focused on the relationship of Aβ with macroglia and microglia, as these glial cells are hypothesized to play important roles in homeostasis and clearance of Aβ in the AD retina. Significantly higher Aβ load was found in AD compared to controls, and specifically in the mid-peripheral region. AD retina showed significantly less immunoreactivity against glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) compared to control eyes. Immunoreactivity against ionized calcium binding adapter molecule-1 (IBA-1), a microglial marker, demonstrated a higher level of microgliosis in AD compared to control retina. Within AD retina, more IBA-1 immunoreactivity was present in the mid-peripheral retina, which contained more Aβ than the central AD retina. GFAP co-localized rarely with Aβ, while IBA-1 co-localized with Aβ in more layers of control than AD donor retina. These results suggest that dysfunction of the Müller and microglial cells may be key features of the AD retina. The online version contains supplementary material available at 10.1186/s40478-022-01448-y.
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