Microbiome and Inherited Retinal Degenerations

Inherited retinal degenerations (IRDs) represent a genetically and clinically heterogeneous group of progressive and visually debilitating disorders that can lead to irreversible visual loss. Our under-standing of IRD pathogenesis at both the genetic and cellular levels has increased tremendously over the past two decades, but the exact pathogenic mechanisms remain incompletely understood. Enhanced understanding of the pathophysiology of these diseases can result in new treatment targets. Alterations in the human gut microbiome play a key role in the pathogenesis of many ocular and nonocular diseases, such as age-related macular degeneration, neurologic and metabolic disorders, and autoim-mune conditions. The gut microbiome regulates the susceptibility of mice to develop experimental autoimmune uveitis, a model for autoimmune disease of the posterior portion of the eye elicited by the systemic response to retinal antigens. Because of the mounting evidence in favor of a role for local and systemic inflammatory and autoimmune-mediated components to IRD pathogenesis, this review pre-sents the current knowledge of gut microbiome in IRDs and discusses the association between possible changes in gut microbiome and pathogenesis of these diseases, with special attention to their possible contribution to the inflammatory underpinnings of IRDs. (Am J Pathol 2023, 193: 1669e1674; https:// doi.org/10.1016/j.ajpath.2023.03.005)