Short-Chain Fatty Acid Mitigates Ocular Surface Inflammation In An Autoimmune Dry Eye Murine Model
Published 2024 - 42nd Congress of the ESCRS
Reference: FP07.10 | Type: Free paper | DOI: 10.82333/nnzg-6q29
Authors: Chung Young Kim* 1 , Seonghwan Kim 2 , Jin Suk Ryu 3 , Wan Jae Choi 3 , Chang Ho Yoon 1 , Mee Kum Kim 1
1Ophthalmology,Seoul National University College of Medicine,Seoul,Korea, Republic Of;Ophthalmology,Seoul National University Hospital,Seoul,Korea, Republic Of;Laboratory of Ocular Regenerative Medicine and Immunology,Biomedical Research Institute, Seoul National University Hospital,Seoul,Korea, Republic Of, 2Ophthalmology,Seoul National University College of Medicine,Seoul,Korea, Republic Of;Laboratory of Ocular Regenerative Medicine and Immunology,Biomedical Research Institute, Seoul National University Hospital,Seoul,Korea, Republic Of;Ophthalmology,Seoul Metropolitan Government Seoul National University Boramae Medical Center,Seoul,Korea, Republic Of, 3Laboratory of Ocular Regenerative Medicine and Immunology,Biomedical Research Institute, Seoul National University Hospital,Seoul,Korea, Republic Of
Purpose
We investigated the effect of butyrate, a short-chain fatty acid (SCFA), on ocular surface inflammation in an autoimmune dry eye murine model.
Setting
Twelve-week-old NOD.B10.H2b mice (n=59) received either a daily 200µL dose of tributyrin or phosphate-buffered saline (PBS) via oral gavage for three weeks. Clinical, histological, and immunological changes in butyrate-treated mice were compared with those in PBS-treated mice.
Methods
This study included treatment-naive C57BL/6 mice as a negative control (n=25) and NOD.B10.H2b mice were divided into PBS (n=28) and butyrate (n=31) groups. After three weeks of oral gavage, disease severity was evaluated using corneal fluorescein staining scores. Histological analysis assessed CD45+ cell infiltration in the lacrimal gland, goblet cell density changes, and the expression of butyrate receptors, as G-protein coupled-receptor (GPR43, GPR109A), in the corneoconjunctiva. Expression levels of inflammatory cytokines in the corneoconjunctiva and lacrimal gland were quantified by RT-PCR. The frequency of conventional or plasmacytoid dendritic cells (DCs) and effector T cells was analyzed via flow cytometry.
Results
Butyrate treatment significantly reduced corneal fluorescein staining scores (P<0.0001). Expression of GPR43 and GPR109A was observed in the cornea of all groups. However, there was no significant difference in lacrimal gland inflammatory score and conjunctival goblet cell density between the PBS and tributyrin groups. In the tributyrin group, the expression levels of IL-1β in the corneoconjunctiva and IL-6 in the lacrimal gland were decreased (P=0.0317, P=0.0357 respectively) compared to the PBS group. The frequency of the plasmacytoid DCs in corneoconjunctiva decreased (P=0.0015) in the tributyrin group.
Conclusions
Butyrate effectively mitigates the severity of dry eye disease, accompanied by the suppression of some innate inflammatory cytokines and a decrease in plasmacytoid DCs on the ocular surface.