Tear Fluid Protein Changes in Dry Eye Syndrome Associated with Rheumatoid Arthritis: A Proteomic Approach.

PURPOSE: Sjögren syndrome (SS) secondary to rheumatoid arthritis (RA) affects lacrimal and salivary glands, and therefore dry eye syndrome (DES) is more prevalent in patients with RA. This study used a proteomic approach to identify potential biomarkers in tear of DES secondary to RA (DES-RA). METHODS: Tear specimens were collected with Schirmer strips from patients with DES with RA, patients with other types of dry eye (namely, primary Sjögrens and non-Sjögrens [NSS]), and age-matched controls. Tear proteins were subjected to 2D-differential gel electrophoresis (2D-DIGE), and the differentially expressed proteins were identified using nano ESI-LC-MS/MS analysis. RESULTS: Among the differentially regulated proteins of DES-RA that were identified, lactotransferrin isoform 1 precursor was found to be d own-regulated in 100% cases and SHC transforming 1 isoform in 63% of the cases, while proteins such as ribonuclease p protein subunit 20, protocadherin, and heterogeneous nuclear ribonucleoprotein Q isoform 6 were down-regulated in over 80% of the cases. Proteins such as Ecto-ADP ribosyltransferase 5 precursor, Rho-related GTP-binding protein, and RhoJ precursor were up-regulated in 80% of the cases. CONCLUSION: Functional annotation revealed that these proteins have roles in regulation, antimicrobial activity, immune, metabolic, and cellular processes. The study observed characteristic marker proteins differentially expressed in DES-RA that are previously unreported. Further validation is needed.

Lacrimal proline rich 4 (LPRR4) protein in the tear fluid is a potential biomarker of dry eye syndrome.

Dry eye syndrome (DES) is a complex, multifactorial, immune-associated disorder of the tear and ocular surface. DES with a high prevalence world over needs identification of potential biomarkers so as to understand not only the disease mechanism but also to identify drug targets. In this study we looked for differentially expressed proteins in tear samples of DES to arrive at characteristic biomarkers. As part of a prospective case-control study, tear specimen were collected using Schirmer strips from 129 dry eye cases and 73 age matched controls. 2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. One of the differentially expressed protein in DES is lacrimal proline rich 4 protein (LPRR4). LPRR4 protein expression was quantified by enzyme immune sorbent assay (ELISA). LPRR4 was down regulated significantly in all types of dry eye cases, correlating with the disease severity as measured by clinical investigations. Further characterization of the protein is required to assess its therapeutic potential in DES.