Yong Woo Ji1,2, Hye Min Kim3, Sun Young Ryu1,2, Jae Won Oh3, Areum Yeo2, Chul Young Choi4, Myoung Joon Kim5, Jong Suk Song6, Hyun Seung Kim7, Kyoung Yul Seo2, Kwang Pyo Kim3, Hyung Keun Lee2,8,9. 1. Department of Ophthalmology, National Health Insurance Service Ilsan Hospital, Goyang, Korea. 2. Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea. 3. Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin, Korea. 4. Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. 5. Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 6. Department of Ophthalmology, Korea University College of Medicine, Seoul, Korea. 7. Department of Ophthalmology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. 8. Institute of Vascular Disease and Metabolism, Yonsei University College of Medicine, Seoul, Korea. 9. College of Pharmacy, Yonsei University, Incheon, Korea.
Abstract
Purpose: To compare the changes in human tear proteome and clinical effects following topical cyclosporine A (CsA) 0.05% or diquafosol tetrasodium (DQS) 3% treatment of dry eye disease (DED), and to identify biomarkers for determining disease severity and treatment effectiveness in DED. Methods: A total of 18 patients were diagnosed with non-Sjögren DED. Nine patients in each group were treated with topical CsA 0.05% or DQS 3% for 4 weeks. Tear samples were collected after evaluation of tear breakup time, corneal and conjunctival erosion staining, and results of Schirmer's test 1 before and after treatment. Proteomes were characterized using liquid chromatography mass spectrometry, and proteins exhibiting a fold change >1.5 or <0.67 (P < 0.05) were considered differentially expressed (DEP). Results: A total of 794 proteins were identified, with no significant difference observed between pretreatment and posttreatment conditions. Proteomic analysis identified 54 and 106 DEPs between treatment groups (CsA and DQS, respectively), with gene ontology analysis indicating that both treatments enhanced innate and adaptive immune responses and cellular detoxification. Protein-network analysis showed that inflammation associated with the immune response was primarily responsible for the therapeutic process in both groups. Conclusions: These results provide insight into the broad scope of changes at the ocular surface in DED and indicated that although both drugs improved the clinical parameters, the activated tear-specific biomarkers differed significantly between treatments. Our findings suggest that the DEPs identified here and those correlated with the clinical parameters might represent candidate biomarkers for DED.
RCT Entities:
Purpose: To compare the changes in human tear proteome and clinical effects following topical cyclosporine A (CsA) 0.05% or diquafosol tetrasodium (DQS) 3% treatment of dry eye disease (DED), and to identify biomarkers for determining disease severity and treatment effectiveness in DED. Methods: A total of 18 patients were diagnosed with non-Sjögren DED. Nine patients in each group were treated with topical CsA 0.05% or DQS 3% for 4 weeks. Tear samples were collected after evaluation of tear breakup time, corneal and conjunctival erosion staining, and results of Schirmer's test 1 before and after treatment. Proteomes were characterized using liquid chromatography mass spectrometry, and proteins exhibiting a fold change >1.5 or <0.67 (P < 0.05) were considered differentially expressed (DEP). Results: A total of 794 proteins were identified, with no significant difference observed between pretreatment and posttreatment conditions. Proteomic analysis identified 54 and 106 DEPs between treatment groups (CsA and DQS, respectively), with gene ontology analysis indicating that both treatments enhanced innate and adaptive immune responses and cellular detoxification. Protein-network analysis showed that inflammation associated with the immune response was primarily responsible for the therapeutic process in both groups. Conclusions: These results provide insight into the broad scope of changes at the ocular surface in DED and indicated that although both drugs improved the clinical parameters, the activated tear-specific biomarkers differed significantly between treatments. Our findings suggest that the DEPs identified here and those correlated with the clinical parameters might represent candidate biomarkers for DED.
Authors: Louis Tong; Li Lim; Donald Tan; Wee Jin Heng; Jimmy Lim; Cordelia Chan; Anshu Arundhati; Anna Tan Journal: Asia Pac J Ophthalmol (Phila) Date: 2021-11-11