Valeric Acid, a Gut Microbiota Product, Penetrates to the Eye and Lowers Intraocular Pressure in Rats

Abstract

Mechanisms controlling intraocular pressure (IOP) and arterial blood pressure (BP) share similar mediators, including gut bacteria metabolites. Here, we investigated the effects of valeric acid (VA), a short chain fatty acid produced by microbiota from undigested carbohydrates, on IOP and BP. To test if gut VA penetrates to the eye we evaluated eyes’ homogenates after the administration of D9-VA into the colon. Additionally, the following experimental series were performed on 16-week-old Sprague Dawley rats to analyze the influence of VA on IOP: vehicle treatment; VA treatment; VA + hydroxybutyrate - a short chain fatty acids’ G protein-coupled receptor 41/43 (GPR 41/43) blocker (ANT); hydroxybutyrate; VA + angiotensin II; angiotensin II; VA treatment in rats with superior cervical ganglion excision and sham operated rats. D9-VA rapidly penetrated from the colon to the eye. VA significantly decreased IOP and BP. The decrease in IOP was gradual and lasted through the experiment. In contrast, a decrease in BP was instantaneous and lasted no longer than 10 min. Angiotensin II, ANT, and sympathetic denervation did not influence the effect of VA on IOP. In conclusion, colon-derived VA penetrates to the eye and decreases IOP. The effect is independent from BP changes, angiotensin II, GPR41/43, and sympathetic eye innervation.