Over the last decade, new evidence has become increasingly more compelling that commensal microflora profoundly influences the maturation and function of resident immune cells in host physiology. The concept of gut-retina axis is actively being explored. Studies have revealed a critical role of commensal microbes linked with neuronal stress, immune responses, and neurodegeneration in the retina. Microbial dysbiosis changes the blood-retina barrier permeability and modulates T cell-mediated autoimmunity to contribute to the pathogenesis of retinal diseases, such as glaucoma. Heat shock proteins (HSPs), which are evolutionarily conserved, are thought to function both as neuroprotectant and pathogenic antigens of T cells contributing to cell protection and tissue damage, respectively. Activated microglia recruit and interact with T cells during this process. Glaucoma, characterized by the progressive loss of retinal ganglion cells, is the leading cause of irreversible blindness. With nearly 70 million people suffering glaucoma worldwide, which doubles the number of patients with Alzheimer’s disease, it represents the most frequent neurodegenerative disease of the central nervous system (CNS). Thus, understanding the mechanism of neurodegeneration in glaucoma and its association with the function of commensal microflora may help unveil the secrets of many neurodegenerative disorders in the CNS and develop novel therapeutic interventions.© 2020 Elsevier B.V. All rights reserved.