Expresssion of CD147 and Cyclophilin A in Dry Eye Disease

摘要

Purpose : CD147 (aka extracellular matrix metalloproteinase inducer, EMMPRIN) are proteins that are known to induce matrix metalloproteinase; however, they have recently been shown to also mediate inflammation in chronic arthritis, acute lung inflammation and cardiovascular disease through interactions with numerous proteins including cyclophilin A (CyPA). Inhibiting CD147 and CyPA interaction using monoclonal antibodies significantly reduced inflammation in those conditions. We hypothesize that CD147 also plays a role in the pathogenesis of dry eye inflammation. The purpose of this study was to characterize the expression of CD147 and CyPA in tears of normal and dry eye patients. Methods : Ocular Surface Disease Index (OSDI) Questionnaire, corneal fluorescein staining, lissamine green conjunctival staining, and cotton red thread test were used to diagnosis dry eye syndrome (DES). Tear samples were collected from 16 subjects (6 normals, 10 DES) using Schirmer strips, cotton threads and/or glass microcapillaries. Differential expression of tear CD147 and CyPA in normal patients and those with DES were tested using western blotting. ELISA assay (R&D Systems) was also performed to determine tear concentration of CD147 in normal and DES. Results : Glycosylated CD147 (55 kDa) was upregulated approximately 30% in subjects with dry eye disease (n=10) compared to normal subjects (n=6), p0.05. Similarly, CyPA (20 kDa) was upregulated by 25% in subjects with severe dry eye disease compared to normal subjects, p0.05. The average concentration of CD147 is 975 pg/ml in normal tears (n=6, range 500-1500 pg/ml) and 2600 pg/ml in DES (n=6, range 1500-4000 pg/ml). Conclusions : Expression of CD147 and CyPA are upregulated in subjects with dry eye disease suggesting that they play a role in the pathogenesis of dry eye inflammation. Further research is needed to determine if these proteins form an association and whether inhibiting this association can provide a therapeutic option in treating dry eye inflammation This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.