Do epigenetic changes caused by commensal microbiota contribute to development of ocular disease? A review of evidence

Abstract

There is evidence that genetic polymorphisms and environmentally induced epigenetic changes play an important role in modifying disease risk. The commensal microbiota has the ability to affect the cellular environment throughout the body without requiring direct contact; for example, through the generation of a pro-inflammatory state. In this review, we discuss evidence that dysbiosis in intestinal, pharyngeal, oral, and ocular microbiome can lead to epigenetic reprogramming and inflammation making the host more susceptible to ocular disease such as autoimmune uveitis, age-related macular degeneration, and open angle glaucoma. Several mechanisms of action have been proposed to explain how changes to commensal microbiota contribute to these diseases. This is an evolving field that has potentially significant implications in the management of these conditions especially from a public health perspective.

Retinitis Pigmentosa Is Associated With Shifts in The Gut Microbiome

“…Initiation and progression of some prevalent retinal neurodegenerative diseases have also been linked to changes in the homeostasis of gut microbiome [33,34]. In our results, sequencing analysis of the gut microbiome in dystrophic and control mice showed differences in alpha and beta diversity and interestingly, these differences were statistically supported at the ASV level.…”

“…Several different mechanisms have been proposed to explain how changes in the gut microbiome are linked to ocular diseases [34]. Microbial imbalance can result in disruptions of the intestinal permeability and the blood-retinal barrier [43], thus allowing bacteria and their products to induce ocular cells to an in ammatory state [34,35]. Moreover, it has been hypothesized that gut dysbiosis may be a cause of increased levels of oxidative stress in the central nervous system [85].…”

“…Moreover, the retina re ects some of the pathological alterations of many neurodegenerative diseases, and may provide information of brain pathology severity [31,32]. In this context, a few recent studies have linked gut microbiome changes with some retinal degenerative diseases [33,34], including age-related macular degeneration (AMD) [35][36][37][38][39], glaucoma [40][41][42][43] and diabetic retinopathy [44], even though the published results vary depending on the type and stage of the disease and between studies. On the other hand, in a previous study we have demonstrated that invasive infection from gastrointestinal microbiome can induce activation of retinal microglia [45], the primary resident immune cell of the retina.…”

T cell-intrinsic role for Nod2 in protection against Th17-mediated uveitis

“…Since host microbiota has been reported to influence T cell development 18 , several Nod2-mediated disease models 9 , as well as pathogenesis of uveitis 19 – 21 , we sought to determine whether Nod2-mediated uveitis was related to altered microbiome due to different housing conditions. To do this, we compared uveitis development in WT and Nod2 −/− mice bred within our facility to newly arrived counterparts shipped directly from The Jackson Laboratory (Supp.…”

Retinitis Pigmentosa is Associated With Shifts in The Gut Microbiome

“…Several different mechanisms have been proposed to explain how changes in the gut microbiome are linked to ocular diseases 34 . Microbial imbalance can result in disruptions of the intestinal permeability and the blood-retinal barrier 43 , thus allowing bacteria and their products to induce ocular cells to an in ammatory state 34,35 . Moreover, it has been hypothesized that gut dysbiosis may be a cause of increased levels of oxidative stress in the central nervous system 79 .…”