The Effect of Chloroquine on the Development of Dry Eye in Sjögren Syndrome Animal Model

• Published in: Investigative ophthalmology & visual science 2019-09, Vol.60 (12), p.3708-3716
• Main Authors: Lee, Hyun Jung, Shin, Soojung, Yoon, Seul-Gi, Cheon, Eun Jeong, Chung, So-Hyang
• Format: Article
• Language: English
• Subjects: Animals; Antirheumatic Agents - pharmacology; Autophagy - drug effects; Autophagy-Related Protein 5 - blood; Biomarkers - metabolism; Chloroquine - pharmacology; Cornea - metabolism; Cornea - pathology; Disease Models, Animal; Dry Eye Syndromes - diagnosis; Dry Eye Syndromes - etiology; Dry Eye Syndromes - prevention & control; Enzyme-Linked Immunosorbent Assay; Female; Goblet Cells - drug effects; Goblet Cells - pathology; Injections, Intraperitoneal; Lacrimal Apparatus - metabolism; Lacrimal Apparatus - pathology; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Microtubule-Associated Proteins - blood; Real-Time Polymerase Chain Reaction; Salivary Glands - metabolism; Salivary Glands - pathology; Sjogren's Syndrome - complications; Sjogren's Syndrome - diagnosis; Sjogren's Syndrome - metabolism; Tears - physiology
• ISSN: 1552-5783; 1552-5783
• 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.