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The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease

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Heparanase

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1221))

Abstract

Homeostasis and visual acuity of the surface of the eye are dependent on tears, a thin film comprising at least 1800 different extracellular proteins and numerous species of lipids through which 80% of entering light is refracted at the air interface. Loss of homeostasis in dry eye disease affects 5–7% of the world’s population, yet little is known about key molecular players. Our story began as an unbiased screen for regulators of tearing that led to the discovery of homeostasis-restorative ‘lacritin’, a tear protein whose active form is selectively deficient in dry eye. Heparanase acts as a novel ‘on-switch’ for lacritin ligation of syndecan-1 necessary to trigger basal tearing, as well as pertussis toxin-sensitive and FOXO-dependent signaling pathways for healing of inflammation-damaged epithelia and restoring epithelial oxidative phosphorylation by mitochondrial fusion downstream of transiently accelerated autophagy. A phase 2 clinical trial has tested the applicability of this mechanism to the resolution of dry eye disease. Results are not yet available. With lacritin proteoforms detected in cerebral spinal fluid, plasma, and urine, the capacity of the lacritin-syndecan-1-heparanase axis to restore homeostasis might have wide systemic relevance to other organs.

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Acknowledgments

The authors acknowledge support to GWL from EY024327, EY026171, the UVa Pinn Scholar Award, 5T32GM08715 (supporting XH) and an unrestricted gift from TearSolutions, Inc.

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Authors and Affiliations

  1. Department of Cell Biology, University of Virginia, Charlottesville, VA, USA

    Karina Dias-Teixeira, Xavier Horton & Jeffrey Romano

  2. School of Integrated Sciences, James Madison University, Harrisonburg, VA, USA

    Robert McKown

  3. Departments of Cell Biology, Biomedical Engineering and Ophthalmology, University of Virginia, Charlottesville, VA, USA

    Gordon W. Laurie

Authors
  1. Karina Dias-Teixeira
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  2. Xavier Horton
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  3. Robert McKown
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  4. Jeffrey Romano
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  5. Gordon W. Laurie
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Correspondence to Gordon W. Laurie .

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Editors and Affiliations

  1. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Israel Vlodavsky

  2. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ralph D. Sanderson

  3. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Neta Ilan

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Dias-Teixeira, K., Horton, X., McKown, R., Romano, J., Laurie, G.W. (2020). The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease. In: Vlodavsky, I., Sanderson, R., Ilan, N. (eds) Heparanase. Advances in Experimental Medicine and Biology, vol 1221. Springer, Cham. https://doi.org/10.1007/978-3-030-34521-1_31

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