Mahajan, Aparna, Hasikova, Lenka ORCID: 0000-0002-4794-2252, Hampel, Ulrike, Grueneboom, Anika, Shan, Xiaomei ORCID: 0000-0002-8799-6335, Herrmann, Irmgard, Garreis, Fabian, Bock, Felix, Knopf, Jasmin, Singh, Jeeshan, Schauer, Christine, Mahajan, Siddharth, Leppkes, Moritz, Paulsen, Friedrich, Schloetzer-Schrehardt, Ursula, Krenn, Veit, Juenemann, Anselm, Hohberger, Bettina, Schett, Georg, Herrmann, Martin and Munoz, Luis E. (2021). Aggregated neutrophil extracellular traps occlude Meibomian glands during ocular surface inflammation. Ocul. Surf., 20. S. 1 - 13. AMSTERDAM: ELSEVIER. ISSN 1937-5913

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Abstract

Purpose: Obstructive Meibomian gland dysfunction (MGD) is one of the leading causes of evaporative dry eye disease. Meibomian glands at the eyelid secrete lipids that prevent evaporation of the aqueous tear film. The pathogenesis of obstructive MGD is incompletely understood to date. Herein, we aim to investigate the pathogenesis of obstructive MGD using murine and human samples with various forms of ocular surface inflammation. Method: The presence of Neutrophil extracellular Traps (NETs) was detected with immunofluorescence analysis of ocular surface discharge and biopsy samples from patients with blepharitis. Tear fluid from patients with MGD and blepharitis were evaluated for the presence of inflammatory mediators using bead based immunoassay. Murine model of allergic eye disease (AED) was performed to investigate the role of NETs in MG occlusion. Results: we show that the ocular discharge from patients with blepharitis contains aggregated neutrophil extracellular traps (aggNETs). Furthermore, the ducts of human Meibomian glands affected by blepharitis were largely congested by aggNETs. Tear fluid from patients with MGD showed elevated neutrophil chemoattractants (C5a, IL6, IL8 and IL18). C5a and IL8 correlated with the degree of deficiency of tear fluid. In the murine model of allergic eye disease (AED), aggNETs accumulated in the MG leading to occlusion of their ducts and the retrograde pent-up of the fluid followed by acinar atrophy. Constraining aggNET formation by genetic or pharmacological inhibition of peptidyl arginine deiminase type 4 (PADI4) effectively reduced MG damage. Conclusion: We conclude that aggNETs occlude MG causing MGD after ocular surface inflammation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mahajan, AparnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hasikova, LenkaUNSPECIFIEDorcid.org/0000-0002-4794-2252UNSPECIFIED
Hampel, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grueneboom, AnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shan, XiaomeiUNSPECIFIEDorcid.org/0000-0002-8799-6335UNSPECIFIED
Herrmann, IrmgardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garreis, FabianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bock, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knopf, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singh, JeeshanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schauer, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mahajan, SiddharthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leppkes, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paulsen, FriedrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schloetzer-Schrehardt, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krenn, VeitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juenemann, AnselmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohberger, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schett, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrmann, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munoz, Luis E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-593736
DOI: 10.1016/j.jtos.2020.12.005
Journal or Publication Title: Ocul. Surf.
Volume: 20
Page Range: S. 1 - 13
Date: 2021
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1937-5913
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DRY EYE; INTERNATIONAL WORKSHOP; DYSFUNCTION REPORT; TEAR CYTOKINE; INTERLEUKIN-8; DISEASE; PATHOPHYSIOLOGY; DEGRANULATION; DEFINITION; ACTIVATIONMultiple languages
OphthalmologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59373

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