Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina

Xu, Qinyuan Alis; Boerkoel, Pierre; Hirsch-Reinshagen, Veronica; Mackenzie, Ian R.; Hsiung, Ging-Yuek Robin; Charm, Geoffrey; To, Elliott F.; Liu, Alice Q.; Schwab, Katerina; Jiang, Kailun; Sarunic, Marinko; Beg, Mirza Faisal; Pham, Wellington; Cui, Jing; To, Eleanor; Lee, Sieun; Matsubara, Joanne A.

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.

Citation

Xu, Q. A., Boerkoel, P., Hirsch-Reinshagen, V., Mackenzie, I. R., Hsiung, G.-Y. R., Charm, G., To, E. F., Liu, A. Q., Schwab, K., Jiang, K., Sarunic, M., Beg, M. F., Pham, W., Cui, J., To, E., Lee, S., & Matsubara, J. A. (2022). Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina. Acta Neuropathologica Communications, 10(1), Article 145. https://doi.org/10.1186/s40478-022-01448-y

• Journal Article Type: Article
• Acceptance Date: Sep 18, 2022
• Online Publication Date: Oct 5, 2022
• Publication Date: Oct 5, 2022
• Deposit Date: Jan 23, 2023
• Publicly Available Date: Jan 24, 2023
• Journal: Acta Neuropathologica Communications
• Electronic ISSN: 2051-5960
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 1
• Article Number: 145
• DOI: https://doi.org/10.1186/s40478-022-01448-y
• Keywords: Research, Retina, Amyloid-β, Alzheimer’s disease, Biomarker, Macroglia, Microglia
• Public URL: https://nottingham-repository.worktribe.com/output/12317797
• Publisher URL: https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-022-01448-y