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Gordon Laurie, Ningning Wang, Robert L McKown, Denise S. Ryan, Rose Kristine Sia, Lamarr Peppers; Differential Availability of Active Lacritin and Cell Targeting Machinery in Normal vs Aqueous Deficient Tears as Insight into Cause. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3680.
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The monomeric form of tear lacritin is a multifunctional factor responsible for alleviating ocular surface stress. It is also an agonist for basal tearing. Monomeric lacritin targets a heparanase (HPSE) deglycanated form of cell surface syndecan-1 (SDC1). However, the lacritin-C splice variant, and lacritin polymerized by tear tissue transglutaminase, are both unable to target SDC1 and are therefore inactive. Here we ask whether either might displace monomeric lacritin in dry eye tears, and if SDC1 or HPSE may be inadequate.
Tears were collected onto Schirmer strips from 146 individuals before and 1 day, 1 week and 1 month after photorefractive keratectomy. Tears were stored at -70 C, and later eluted with a tear equivalent volume of PBS, and pooled by time and normal (≥ 15mm) vs dry eye (≤ 5 mm) tears. Tears were separated by SDS-PAGE and blotted with anti-N-terminal specific lacritin mab 1F5, anti-C-terminal specific lacritin ab ‘ab C-term’, anti-lacritin-C splice variant mab 4F6, anti-SDC1 mab A-38B, and with anti-heparanase abs #733 and #1453. Secondary abs were precleared over a tear column, and ab C-term was precleared over C-59 lacritin truncation mutant.
Ab C-term detected less lacritin monomer in dry eye vs normal tears, a deficiency apparently compensated in dry eye by enhanced lacritin-C splice variant. The 1F5 mab epitope is shared by both forms, and thus the presumed hybrid band appeared greater in dry eye. Normal tears were enriched in latent (uncleaved) HPSE and deglycanated SDC1. 1 day after PRK, lacritin-C was further increased in dry eye, and both SDC1 and HPSE less in normals. Return to pre-PRK conditions was apparent by 1 month.
Aqueous deficient dry eye tears are associated with decreased lacritin monomer, increased lacritin-C splice variant, and less deglycanted SDC1 and latent HPSE. These conditions are appropriate for the exacerbation or initiation of dry eye.
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