Department of Ophthalmology and Visual Science, Catholic Institute of Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Biochemical Engineering, Seoil University, Seoul, Korea.
Invest Ophthalmol Vis Sci. 2019 Sep 3;60(12):3708-3716. doi: 10.1167/iovs.19-27469.
Sjögren syndrome (SS) is an autoimmune disease characterized by the inflammatory destruction of salivary and lacrimal glands (LG). Chloroquine (CQ) was known as an immunomodulatory drug and in the inhibition of autophagy. The purpose of the study is to investigate the effect of CQ on the development of dry eye in NOD-LtJ mice.
NOD-LtJ mice were observed, during which the occurrence of dry eye was confirmed by tear secretion, corneal staining, and the infiltration of foci into the LG from 13-week-old mice. Intraperitoneal (IP) administration of CQ was performed in 13-week-old mice for 4 weeks and maintained untreated for another 4 weeks. Additionally, CQ was injected IP in 19-week-old mice for 2 weeks from when the disease was fully developed.
Interestingly, the expression of autophagy marker ATG5 and LC3B-II was observed in the LG from week 5. When CQ had been administered for 4 weeks from week 13 and then maintained untreated for 4 weeks, tear secretion, corneal staining score, foci formation in the LG, conjunctival goblet cells and proinflammatory cytokine expressions were significantly better than untreated mice. The infiltration of immune cells and the expression of autophagy markers in LG were decreased in the CQ group. These indices improved significantly as well when the 19-week-old mice with severe clinical phenotypes had been treated with CQ for 2 weeks.
This study demonstrated that autophagy was induced in the early stages of the SS model and that CQ treatment in the early stages could inhibit disease progression.
干燥综合征（SS）是一种自身免疫性疾病，其特征是唾液腺和泪腺（LG）的炎症破坏。氯喹（CQ）已知具有免疫调节作用，并能抑制自噬。本研究旨在探讨 CQ 对 NOD-LtJ 小鼠干眼症发展的影响。
观察 NOD-LtJ 小鼠，从 13 周龄小鼠开始，通过泪液分泌、角膜染色和 LG 灶浸润来确认干眼症的发生。从 13 周龄开始，对 CQ 进行腹腔（IP）给药 4 周，并保持未治疗状态 4 周。此外，在疾病完全发展时，从 19 周龄开始，将 CQ 通过 IP 注射 2 周。
有趣的是，从第 5 周开始就在 LG 中观察到自噬标记物 ATG5 和 LC3B-II 的表达。从第 13 周开始 CQ 治疗 4 周，然后保持未治疗状态 4 周时，泪液分泌、角膜染色评分、LG 灶形成、结膜杯状细胞和促炎细胞因子表达均明显优于未治疗的小鼠。LG 中免疫细胞的浸润和自噬标志物的表达在 CQ 组中减少。当 19 周龄具有严重临床表型的小鼠用 CQ 治疗 2 周时，这些指标也显著改善。
本研究表明，自噬在 SS 模型的早期阶段被诱导，早期 CQ 治疗可以抑制疾病进展。
