The gut-retina axis plays a role in glaucoma autoimmunity, with altered gut microbiota in glaucoma patients triggering peripheral immune responses, according to research.
The gut-brain axis has been widely studied in central nervous system diseases, suggesting that gut microbiota can influence neurological conditions. Similarly, the concept of the gut-retina axis has been proposed to explain autoimmune responses in the eye.
“Approximately half of glaucoma patients have normal intraocular pressure (IOP). Moreover, some patients with elevated IOP continue to experience ongoing loss of retinal ganglion cells (RGCs) and optic nerve injury even after their IOP returns to normal. This suggests that alternative mechanisms other than IOP may contribute to the development of glaucoma,” investigators explained in Heliyon.
Studies have found significant differences in the gut microbiota of glaucoma patients, including increased quantities of Firmicutes, Bacteroidetes, Proteobacteria, Prevotellaceae, Enterobacteriaceae, Dysgonamonadaceae, Lactobacillus, and Escherichia coli, and decreased quantities of Baresiellaceae, Megamonas, Mollicutes, and Bacteroides plebeius.
“Furthermore,” noted the investigators, “a meta-analysis reveals that Helicobacter pylori infection is associated with primary open-angle glaucoma and normal-tension glaucoma.” These alterations may activate peripheral immune responses that contribute to glaucoma progression.
Antigens from these gut bacteria can prime peripheral T cells, which then cross the blood-retina barrier (BRB) and initiate autoimmune damage to RGCs through molecular mimicry. The researchers discussed several other mechanisms by which T cells are implicated in RGC damage: Chronic ocular inflammation that is driven by activated glial cells is also essential for persistent T-cell transmigration across the BRB. Additionally, elevated levels of pro-inflammatory cytokines have been documented in the aqueous humor and tears of glaucoma patients, facilitating ongoing RGC damage.
The review noted the presence of elevated autoantibodies in the serum of glaucoma patients that target ocular antigens. This mechanism is not yet understood and requires additional research.
“The proposal of this perspective holds significant implications for understanding the pathogenesis of glaucoma, developing novel therapeutic strategies, and potentially altering the clinical management of the disease,” the researchers noted.
Autoantibody profiles could be valuable biomarkers for early detection and monitoring of glaucoma, while immunomodulatory therapies targeting specific immune pathways may enhance current treatments; further research should validate these approaches and explore combination therapies addressing both intraocular pressure and autoimmune mechanisms.
A full list of author disclosures can be found in the published research.
