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To identify and characterize the underlying molecular and cellular components involved in the immunopathology in dry eye disease (DED), we profiled a large number of immune mediators and other protein factors of potential immunopathological relevance in tears from DED patients, and characterized potential underlying mechanisms and patient heterogeneity with multivariate systems biology approach.We report here the identification of unique protein biomarker signatures in the tear film of DED patients and specific pathways and potential molecular mechanisms that these biomarker signatures are known to be associated with.We will also discuss how the new findings of tear biomarker signature could be used to facilitate better diagnosis and management of DED.