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Published on: November 22, 2024
Exosomes from Limosilactobacillus fermentum Ameliorate Benzalkonium Chloride-Induced Inflammation in Conjunctival
Kippeum Lee1, Hyeonjun Gwon1, Joo Yun Kim1
1R&BD Center, Hy Co., Ltd., 22 Giheungdanji-ro 24 Beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea.
Abstract:
Dry eye is characterized by persistent instability and decreased tear production, which are accompanied by epithelial lesions and inflammation on the surface of the eye. In our previous paper, we reported that supplementation with Limosilactobacillus fermentum HY7302 (HY7302) could inhibit corneal damage in a benzalkonium chloride (BAC)-induced mouse model of dry eye, through its effects in gut microbiome regulation. The aim of this study was to determine what functional extracellular substances can alter the inflammatory response of conjunctival cells. We isolated exosomes from HY7302 probiotic culture supernatant, analyzed their morphological characteristics, and found that their average size was 143.8 ± 1.1 nm, which was smaller than the exosomes from the L. fermentum KCTC 3112 strain. In addition, HY7302-derived exosomes significantly reduced the levels of genes encoding pro-inflammatory cytokines, including interleukin (IL)-20, IL-8, IL-6, and IL-1B, in BAC-treated human conjunctival cells. Moreover, HY7302-derived exosomes significantly increased the levels of genes encoding tight junction proteins, including TJP1, TJP2, and occludin-1, in Caco-2 cells. Lastly, the HY7302 exosomes reduced mRNA expression levels of IL1B, IL20, IL6, IL8, and NFAT5 in a transwell coculture system. Our findings indicate that HY7302 exosomes have potential for use in the treatment of ocular inflammation-related dry eye disease, through gut-eye axis communication via exosomes.
Insights
Exosomes from the probiotic Limosilactobacillus fermentum HY7302 can treat dry eye. These exosomes reduce ocular inflammation and improve gut-eye axis communication, offering a novel therapeutic approach for dry eye disease.
Area of Science:
- Microbiology and Immunology
- Ocular Surface Disease
- Gut-Eye Axis Research
Background:
- Dry eye disease involves ocular surface inflammation and tear instability.
- Previous research indicated Limosilactobacillus fermentum HY7302 (HY7302) benefits dry eye via gut microbiome modulation.
- The role of specific extracellular substances in modulating conjunctival cell inflammation requires investigation.
Purpose of the Study:
- To identify functional extracellular substances from HY7302 that can alter conjunctival cell inflammatory responses.
- To investigate the therapeutic potential of HY7302-derived exosomes in dry eye disease models.
Main Methods:
- Isolation and characterization of exosomes from HY7302 probiotic culture supernatant.
- Assessment of exosome effects on pro-inflammatory cytokine gene expression in benzalkonium chloride (BAC)-treated human conjunctival cells.
- Evaluation of exosome impact on tight junction protein gene expression in Caco-2 cells.
- Analysis of exosome effects on inflammatory gene and NFAT5 expression in a transwell coculture system.
Main Results:
- HY7302-derived exosomes (average size 143.8 ± 1.1 nm) significantly reduced pro-inflammatory cytokine gene expression (IL-20, IL-8, IL-6, IL-1B) in BAC-treated conjunctival cells.
- These exosomes increased the expression of tight junction proteins (TJP1, TJP2, occludin-1) in Caco-2 cells.
- HY7302 exosomes decreased mRNA levels of IL1B, IL20, IL6, IL8, and NFAT5 in a coculture system, suggesting modulation of the gut-eye axis.
Conclusions:
- Exosomes derived from Limosilactobacillus fermentum HY7302 possess anti-inflammatory properties relevant to dry eye disease.
- These exosomes may exert therapeutic effects by modulating ocular inflammation and enhancing epithelial barrier function via the gut-eye axis.
- HY7302 exosomes represent a promising novel therapeutic agent for ocular inflammation-associated dry eye.
