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阿尔茨海默病视网膜中的 Müller 细胞变性和小胶质细胞功能障碍。

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

机构信息

MD Undergraduate Program, University of British Columbia, Vancouver, BC, Canada.

Postgraduate Medical Education, Department of Family and Community Medicine, University of Toronto, Barrie, ON, Canada.

出版信息

Acta Neuropathol Commun. 2022 Oct 5;10(1):145. doi: 10.1186/s40478-022-01448-y.

DOI:10.1186/s40478-022-01448-y
PMID:36199154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9533552/
Abstract

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.

摘要

淀粉样蛋白 β (Aβ) 在阿尔茨海默病 (AD) 眼中的视网膜沉积可能为 AD 提供有用的诊断生物标志物。本研究主要关注 Aβ 与大胶质细胞和小胶质细胞的关系,因为这些神经胶质细胞被认为在 AD 视网膜中 Aβ 的内稳态和清除中发挥重要作用。与对照组相比,AD 中 Aβ 的负荷明显更高,特别是在中周边区域。与对照组相比,AD 视网膜对神经胶质纤维酸性蛋白 (GFAP) 和谷氨酰胺合成酶 (GS) 的免疫反应性明显降低。与小胶质细胞标志物离子钙结合衔接蛋白-1 (IBA-1) 的免疫反应性相比,AD 视网膜中的小胶质细胞增生水平更高。在 AD 视网膜中,更多的 IBA-1 免疫反应性存在于中周边视网膜,该区域的 Aβ 含量高于中央 AD 视网膜。GFAP 与 Aβ 很少共定位,而 IBA-1 在对照组供体视网膜的更多层与 Aβ 共定位。这些结果表明,Müller 胶质细胞和小胶质细胞的功能障碍可能是 AD 视网膜的关键特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/201f746cd11a/40478_2022_1448_Fig13_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/201f746cd11a/40478_2022_1448_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/147841d4dd2f/40478_2022_1448_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/18838a3a95ed/40478_2022_1448_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/ce862fb93071/40478_2022_1448_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/33a1eec11a7c/40478_2022_1448_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/ff8f0809bb8b/40478_2022_1448_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/d416afd60876/40478_2022_1448_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/6a566e9d85d6/40478_2022_1448_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/f817988015ad/40478_2022_1448_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/c048759a4a22/40478_2022_1448_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/6985e8d2b86b/40478_2022_1448_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/215cfd5aa2df/40478_2022_1448_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/9533552/201f746cd11a/40478_2022_1448_Fig13_HTML.jpg

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