Changes in human tear proteome following topical treatment of dry eye disease: Cyclosporine a versus diquafosol tetrasodium

Yong Woo Ji, Hye Min Kim, Sun Young Ryu, Jae Won Oh, Areum Yeo, Chul Young Choi, Myoung Joon Kim, Jong Suk Song, Hyun Seung Kim, Kyoung Yul Seo, Kwang Pyo Kim, Hyung Keun Lee

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)5035-5044
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Issue number15
Publication statusPublished - 2019 Dec 1

Bibliographical note

Funding Information:
The authors thank Kazuo Tsubota for giving valuable advice and comments on the study design and data analysis. Supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) (NRF-2018R1C1B6002106 and NRF-2018R1A2B3001110) and the Nano-Material Technology Development Program through the NRF and funded by the Korea government (Ministry of Science and ICT) (NRF-2017M3A7B4041798). Disclosure: Y.W. Ji, None; H.M. Kim, None; S.Y. Ryu, None; J.W. Oh, None; A. Yeo, None; C.Y. Choi, None; M.J. Kim, None; J.S. Song, None; H.S. Kim, None; K.Y. Seo, None; K.P. Kim, None; H.K. Lee, None

Publisher Copyright:
© 2019 The Authors j ISSN: 1552-5783

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Changes in human tear proteome following topical treatment of dry eye disease: Cyclosporine a versus diquafosol tetrasodium'. Together they form a unique fingerprint.

Cite this