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Meredith Stallone, Sonal Sathe, Tracy Thuy Nguyen; CD147 and extracellular Cyplophilin A form a complex in dry eye tear film. Invest. Ophthalmol. Vis. Sci. 2017;58(8):446.
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© ARVO (1962-2015); The Authors (2016-present)
Previous data collected in our lab showed that secreted CD147 (aka extracellular matrix metalloproteinase inducer, EMMPRIN) and eCyPA (extracellular cyclophilin A) are upregulated in the tear film of subjects with dry eye inflammation. CD147 has been identified as the primary receptor for extracellular cyclophilins. This interaction has been shown to be proinflammatory due to increased chemotactic activity. Inhibiting CD147 and CyPA interaction using CD147 monoclonal antibodies reduced inflammation by 50% in acute and chronic lung inflammation and rheumatoid arthritis. The purpose of this study was to establish whether CD147 and eCyP form a protein complex in the tear film of normal subjects and subjects with dry eye syndrome (DES).
Tear samples were collected from both normal and dry eye subjects using either glass microcapillaries or cotton threads. Ocular Surface Disease Index (OSDI) Questionnaire, corneal fluorescein staining, lissamine green conjunctival staining, and tear secretion with cotton threads were used to diagnose subjects with DES. Immunoprecipitation was performed using Dynabeads® Protein G and CD147 antibody. The elutant protein was analyzed by Western blotting using anti-CyPA and CyPB antibodies.
Extracellular Cyclophilin A formed a complex with CD147 in 3 tear samples collected from a dry eye subject. In contrast, no CD147-eCyPA complex was found in the 3 tear samples of a normal subject. Cyclophilin B and CD147 did not associate in tear samples of either the normal or dry eye subject.
CD147 and CyPA form a complex in tear samples of a dry eye but not normal subject. Processing of more tear samples are needed to confirm this finding. However, preliminary results suggest that CD147-eCyPA interaction plays a role in the pathogenesis of dry eye inflammation. Inhibiting this association may provide a therapeutic option in treating dry eye inflammation. Further research is needed to understand the signaling transduction pathway initiated by CD147-eCyPA interaction.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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