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

Authors
 Yong Woo Ji  ;  Hyun Goo Kang  ;  Jong Suk Song  ;  Ji Won Jun  ;  Kyusun Han  ;  Tae-Im Kim  ;  Kyoung Yul Seo  ;  Hyung Keun Lee 
Citation
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.62(4) : 14, 2021-04 
Journal Title
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 
ISSN
 0146-0404 
Issue Date
2021-04
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-γ, IL-17, and TNF-α 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.
Files in This Item:
T202101469.pdf Download
DOI
10.1167/iovs.62.4.14
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyun Goo(강현구) ORCID logo https://orcid.org/0000-0001-8359-9618
Kim, Tae-Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
Seo, Kyoung Yul(서경률) ORCID logo https://orcid.org/0000-0002-9855-1980
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
Ji, Yong Woo(지용우) ORCID logo https://orcid.org/0000-0002-7211-6278
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182866
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