In recent years, microbiota-associated neurodegenerative diseases have been exploited and provided new insight into disease pathogenesis. However, primary open-angle glaucoma (POAG), known as a complex neurodegenerative disease resulting from retinal ganglion cell death and optic nerve damage, can cause irreversible blindness and visual field loss. POAG, which shares several similarities with Parkinson’s disease (PD) and Alzheimer’s disease (AD), has limited studies and slow progression in the understanding of pathogenesis when compared to PD and AD. In this review, we summarized the current knowledge of POAG and commensal microbiota, combined with several lines of evidence in PD and AD to propose a possible hypothesis for POAG pathogenesis: microorganisms cause glaucoma via gut–retina axis, resulting in autoantibodies and autoreactive T cells that lead to autoimmunity. Furthermore, dual-hit hypothesis, an example of a commensal pathogen that causes PD, was partially exported in POAG. Finally, future perspectives are suggested to expand understanding of POAG.
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