Abstract
Purpose :
Primary Open Angle Glaucoma (POAG) is one of the leading causes of blindness worldwide. With limited therapeutics targeting the site of pathogenesis at the trabecular meshwork (TM) site, new molecular targets are greatly needed. The human microbiome has been implicated in the development of many diseases. Recently, microbial by-products of commensal bacteria such as short-chain fatty acids (acetate, butyrate, and propionate) have been shown to have therapeutic effects on ocular tissues. Here we show that butyrate protects against the fibrotic effects of Transforming Growth Factor Beta-2 (TGFb-2).
Methods :
In this study, we treated human and mouse TM cells with (TGFb-2, 5ng/mL) in the presence or absence of butyrate (1.25 uM) and evaluated the expression of extracellular matrix proteins. We performed immunofluorescence imaging, qPCR, and western blot to evaluate the expression of these extracellular matrix proteins.
Results :
Butyrate, a byproduct of commensal bacteria, was shown to have anti-fibrotic properties. We show that human and mouse TM cells exposed to TGFb-2 are protected by butyrate by blocking the production of Fibronectin, Collagen-1 and Collagen-4 via gene expression (p-value < .05), immunofluorescence, and western blot (p-value < .05).
Conclusions :
These important findings provide a novel role for butyrate as a potential therapeutic for the treatment of POAG. Current studies are underway to elucidate the molecular target of butyrate and the potential use of other short-chain fatty acids in TM cells.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.