Muller cell degeneration and microglial dysfunction in the Alzheimer's retina.
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ABSTRACT:
SUBMITTER: Xu QA
PROVIDER: S-EPMC9533552 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.
Xu Qinyuan Alis QA Boerkoel Pierre P Hirsch-Reinshagen Veronica V Mackenzie Ian R IR Hsiung Ging-Yuek Robin GR Charm Geoffrey G To Elliott F EF Liu Alice Q AQ Schwab Katerina K Jiang Kailun K Sarunic Marinko M Beg Mirza Faisal MF Pham Wellington W Cui Jing J To Eleanor E Lee Sieun S Matsubara Joanne A JA
Acta neuropathologica communications 20221005 1
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 fi ...[more]
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Project description:The eye is continuously under oxidative stress due to high metabolic activity and reactive oxygen species generated by daily light exposure. The redox-sensitive protein DJ-1 has proven to be essential in order to protect retina and retinal pigment epithelium (RPE) from oxidative-stress-induced degeneration. Here, we analyzed the specific role of Müller cell DJ-1 in the adult zebrafish retina by re-establishing Müller-cell-specific DJ-1 expression in a DJ-1 knockout retina. Loss of DJ-1 resulted in an age-dependent retinal degeneration, including loss of cells in the ganglion cell layer, retinal thinning, photoreceptor disorganization and RPE cell dysfunction. The degenerative phenotype induced by the absence of DJ-1 was inhibited by solely expressing DJ-1 in Müller cells. The protective effect was dependent upon the cysteine-106 residue of DJ-1, which has been shown to be an oxidative sensor of DJ-1. In a label-free proteomics analysis of isolated retinas, we identified proteins differentially expressed after DJ-1 knockout, but with restored levels after Müller cell DJ-1 re-insertion. Our data show that Müller cell DJ-1 has a major role in protecting the retina from age-dependent oxidative stress.
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