July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Relative Deficiency of Active Lacritin, the Shed Form of Lacritin Co-Receptor Syndecan-1 and the Pro-Form of Syndecan-Activating Enzyme Heparanase in Dry Eye Tears, and Development of a Tear Interactome
Author Affiliations & Notes
  • Gordon W Laurie
    Cell Biology, University of Virginia, Charlottesville, Virginia, United States
  • Jeff Romano
    Cell Biology, University of Virginia, Charlottesville, Virginia, United States
  • Leran Mao
    Cell Biology, University of Virginia, Charlottesville, Virginia, United States
  • Karina Luiza Dias Teixeira
    Cell Biology, University of Virginia, Charlottesville, Virginia, United States
  • Robert L McKown
    Integrated Science and Technology, James Madison University, Harrisonburg, Virginia, United States
  • Denise Ryan
    Warfighter Refractive Eye Surgery Program and Research Center, Fort Belvoir, Fort Belvoir, Virginia, United States
  • Bruce Rivers
    Warfighter Refractive Eye Surgery Program and Research Center, Fort Belvoir, Fort Belvoir, Virginia, United States
  • Footnotes
    Commercial Relationships   Gordon Laurie, TearSolutions, Inc. (F), UVa Licensing and Ventures Group (P); Jeff Romano, None; Leran Mao, None; Karina Luiza Dias Teixeira, None; Robert McKown, TearSolutions, Inc. (R); Denise Ryan, None; Bruce Rivers, None
  • Footnotes
    Support  NIH EY024327 (to GWL)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3828. doi:https://doi.org/
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      Gordon W Laurie, Jeff Romano, Leran Mao, Karina Luiza Dias Teixeira, Robert L McKown, Denise Ryan, Bruce Rivers; Relative Deficiency of Active Lacritin, the Shed Form of Lacritin Co-Receptor Syndecan-1 and the Pro-Form of Syndecan-Activating Enzyme Heparanase in Dry Eye Tears, and Development of a Tear Interactome. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3828. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Lacritin is a basal tear and homeostasis promoting factor in tears whose activity is concentrated in its C-terminus - the latter represented in tears as a naturally processed fragment similar to the synthetic peptide currently in a Phase 2 trial for Sjögren's syndrome dry eye. Lacritin targets cells via a novel 'off/on switch' by which heparanase exposes a latent binding site in syndecan-1 that thereafter is unstable and is likely shed into tears. Here we analyze basal normal and dry eye tears for relative levels of lacritin, C-terminal fragment, lacritin-C splice variant, heparanase and syndecan-1. We also develop the first lacritin tear interactome.

Methods : Relative levels of lacritin, lacritin-C splice variant, heparanase and syndecan-1 in SDS-PAGE separated basal tears from normal and aqueous dry eye individuals were analyzed by LI-COR. Lacritin interactors were detected by Biogrid, Bioplex, IntAct, String, Mentha and PCViz for analysis by Cytoscape.

Results : Active lacritin monomer and C-terminal fragment were equally well-represented in normal tears, but deficient in dry eye, as was the lacritin-C splice variant of unknown function, and syndecan-1. A similar pattern was observed for pro- and active forms of heparanase. The predicted lacritin interactome consists of 47 proteins that differed in multiple forms of dry eye.

Conclusions : Deficiency of active lacritin monomer and C-terminal fragment may underlie lack of shed syndecan-1 in dry eye. Why the pro form of heparanase is apparently downregulated is unknown. Overall, lacritin may have a substantial influence on the tear proteome, beyond its role as an inflammation-insensitive secretory agonist for lipocalin-1 and lactoferrin.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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