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Mechanisms controlling intraocular pressure (IOP) and arterial blood pressure (BP) sharesimilar mediators, including gut bacteria metabolites. Here, we investigated the effects of valericacid (VA), a short chain fatty acid produced by microbiota from undigested carbohydrates, on IOPand BP. To test if gut VA penetrates to the eye we evaluated eyes' homogenates after theadministration of D9-VA into the colon. Additionally, the following experimental series wereperformed on 16-week-old Sprague Dawley rats to analyze the influence of VA on IOP: vehicletreatment; VA treatment; VA + hydroxybutyrate - a short chain fatty acids' G protein-coupledreceptor 41/43 (GPR 41/43) blocker (ANT); hydroxybutyrate; VA + angiotensin II; angiotensin II; VAtreatment in rats with superior cervical ganglion excision and sham operated rats. D9-VA rapidlypenetrated from the colon to the eye. VA significantly decreased IOP and BP. The decrease in IOPwas gradual and lasted through the experiment. In contrast, a decrease in BP was instantaneous andlasted no longer than 10 min. Angiotensin II, ANT, and sympathetic denervation did not influencethe 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 eyeinnervation.

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