Dataset Information

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

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.

SUBMITTER: Dias-Teixeira K

PROVIDER: S-EPMC7398572 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Dias-Teixeira Karina K Horton Xavier X McKown Robert R Romano Jeffrey J Laurie Gordon W GW

Advances in experimental medicine and biology 20200101

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 'la ...[more]

PMID: 32274735

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Project description:BackgroundDry eye disease (DED), Meibomian gland dysfunction (MGD), and Sjögren's syndrome dry eye disease (SS-DED) are eye dryness conditions that show significant overlap in various symptoms of ocular discomfort. The aim of this study was to qualitatively explore the patient experience and evaluate content validity of the newly developed Dry Eye Disease Questionnaire (DED-Q).MethodsSemi-structured interviews were conducted with 61 US adults who reported experiencing ocular symptoms due to their physician-confirmed primary diagnosis of DED (n = 21), MGD (n = 20), or SS-DED (n = 20). The open-ended concept-elicitation phase was followed by cognitive debriefing (CD) of the DED-Q to evaluate participants' understanding and relevance of the instructions, items, response options, and recall periods. Interviews were also conducted with eight specialist healthcare professionals to assess clinical relevance of the concepts included. Verbatim interview transcripts were analyzed using thematic analysis in ATLAS.ti v8 software.ResultsA total of 29 symptoms and 14 impacts on quality of life were reported across participant interviews. Primary ocular symptoms reported included eye dryness (n = 61/61; 100%), eye irritation (n = 55/61; 90%), eye itch (n = 54/61; 89%), burning sensation (n = 52/61; 85%), and foreign body sensation (n = 51/61; 84%). The most impacted aspects of daily life were using digital screens (n = 46/61; 75%), driving (n = 45/61; 74%), working (n = 39/61; 64%), and reading (n = 37/61; 61%). CD findings showed most participants had good understanding of DED-Q items and confirmed most concepts were relevant to the lived experience of their condition. Aside from few minor changes to the items and examples to facilitate more accurate interpretation, the proposed instruction wording was modified for various symptom and impact modules to encourage participants to focus only on dry eye vision problems.ConclusionsThis research identified multiple prevalent symptoms and impacts of DED, MGD, and SS-DED, most of which were similar across the conditions. The DED-Q was confirmed to be a content-valid PRO measure suitable for use in clinical studies to assess the patient experience of DED, MGD, and SS-DED. Future work will focus on evaluating the psychometric properties of the DED-Q for use as an efficacy endpoint in clinical trials.

Dataset Information

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

Publications

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

Similar Datasets

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