Oral Tributyrin Supplementation Mitigates Ocular Surface Inflammation in Age-Related Dry Eye Disease

Abstract

Purpose : This study investigates the potential impact of butyrate, in the form of tributyrin, on mitigating ocular surface inflammation in age-related dry eye disease.

Methods : The study included C57BL/6 mice in both young age (8 weeks, negative control, n=21) and old age (1–2 years old, n=40). Old age mice underwent either PBS treatment (n=19) or tributyrin treatment (n=21) for 21 days. Disease severity was evaluated using corneal fluorescein staining scores. Inflammatory changes in lacrimal gland tissue were examined through histological analysis of inflammatory foci scoring. Levels of inflammatory cytokines in the corneoconjunctiva and lacrimal gland were quantified using PCR, and lymphocyte dynamics were assessed via flow cytometry.

Results : Tributyrin treatment significantly reduced corneal fluorescein staining scores in aged mice. Inflammatory foci scores increased in lacrimal gland of the PBS treated aged mice but not in the tributyrin-treated group. Among the assayed inflammatory cytokines, IL-6 and IL-17A decreased significantly in the tributyrin-treated group. Flow cytometry analysis revealed an increase in CD45⁺ lymphocytes in PBS-treated aged mice. CD3⁺INF-γ⁺ and CD3⁺IL-17A⁺ T cells showed an increase in PBS-treated aged mice but demonstrated a decrease in the tributyrin-treated group. Furthermore, CD11b⁺CD11c⁺CD86⁺MHCII⁺ dendritic cells were elevated in the ocular surface of the PBS-treated group. CD3⁺CD4⁺CD25⁺Foxp3⁺ regulatory T cells decreased in the PBS-treated group but not in the tributyrin-treated group.

Conclusions : Oral supplementation of tributyrin effectively mitigates the severity of age-related dry eye disease, accompanied by the suppression of specific inflammatory cytokines and alterations in the dynamics of dendritic cells and T cells on the ocular surface.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.