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The Dopaminergic Neuronal System Regulates the Inflammatory Status of Mouse Lacrimal Glands in Dry Eye Disease

Authors
Ji, Yong WooKang, Hyun GooSong, Jong SukJun, Ji WonHan, KyusunKim, Tae-imSeo, Kyoung YulLee, Hyung Keun
Issue Date
4월-2021
Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Keywords
dry eye disease; dopamine; dopamine receptor; lacrimal gland
Citation
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v.62, no.4
Indexed
SCIE
SCOPUS
Journal Title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume
62
Number
4
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/128348
DOI
10.1167/iovs.62.4.14
ISSN
0146-0404
Abstract
PURPOSE. Comparison of the parasympathetic and sympathetic neurons, including the dopaminergic neural system, in dry eye (DE)-induced pathophysiology has not been elucidated well. This study investigated the presence of dopamine receptors (DRs) and their functional roles in the lacrimal glands (LGs) of DE-induced mice. METHODS. After DE was induced in B6 mice for 2 weeks, the expression of tyrosine hydroxylase (TH), dopamine, and DRs (DR1, DR2, etc.) in the LGs and corneas were measured by quantitative RT-PCR, immunoblot, and ELISA. Using flow cytometry and ELISA, immune cell infiltration and inflammatory cytokine expression were determined in DE-induced LGs with or without DR blockers, SCH-23390 (DR1i), or melperone (DR2i). Corneal erosion scores were also investigated. RESULTS. The mRNA and protein levels of TH significantly increased in DE-induced LGs. The dopamine concentration of LGs was 9.51 pmol in DE (versus naive: 1.39 pmol; P < 0.001). Both DR1 and DR2 mRNA expression were significantly enhanced in desiccating stress compared with those in naive (3.7- and 2.1-fold, P < 0.001). Interestingly, DR1 and DR2 immunostaining patterns stained independently in DE-induced LGs. CD3(+) and CD19(+) cell infiltration was significantly increased by DR2i (P < 0.001) but not by DR1i. Furthermore, IFN-gamma, IL-17, and TNF-alpha were significantly upregulated by DR2i compared with the blow-only condition. The severity of corneal erosion and inflammation was also aggravated by DR2i. CONCLUSIONS. Upregulation of DR1 and DR2 was observed in DE-induced mouse LGs. As the inflammatory conditions are aggravated by the inhibition of DRs, especially DR2, their activity may be an important factor preserving ocular surface homeostasis.
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