Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Erlangen, Germany.
Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Erlangen, Germany; Department of Rheumatology, First Faculty of Medicine, Charles University-Institute of Rheumatology Prague, Czech Republic.
Ocul Surf. 2021 Apr;20:1-12. doi: 10.1016/j.jtos.2020.12.005. Epub 2021 Jan 2.
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.
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.
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.
We conclude that aggNETs occlude MG causing MGD after ocular surface inflammation.
阻塞性睑板腺功能障碍（MGD）是蒸发性干眼症的主要原因之一。眼睑的睑板腺分泌脂质，防止水样泪膜蒸发。阻塞性 MGD 的发病机制迄今尚未完全了解。在此，我们旨在使用各种形式的眼表炎症的鼠和人样本研究阻塞性 MGD 的发病机制。
通过对睑缘炎患者的眼部分泌物和活检样本进行免疫荧光分析，检测中性粒细胞细胞外陷阱（NETs）的存在。使用基于珠的免疫测定法评估 MGD 和睑缘炎患者的泪液中是否存在炎症介质。进行过敏性眼病（AED）的小鼠模型研究以研究 NETs 在 MG 闭塞中的作用。
我们表明，睑缘炎患者的眼部分泌物中含有聚集的中性粒细胞细胞外陷阱（aggNETs）。此外，受睑缘炎影响的人睑板腺导管大部分被 aggNETs 充血。MGD 患者的泪液中显示出升高的中性粒细胞趋化因子（C5a、IL6、IL8 和 IL18）。C5a 和 IL8 与泪液缺乏程度相关。在过敏性眼病（AED）的小鼠模型中，aggNETs 在 MG 中积累，导致其导管阻塞，随后逆行积聚液体导致腺泡萎缩。通过基因或药理学抑制肽基精氨酸脱亚氨酶 4（PADI4）来限制 aggNET 形成可有效减轻 MG 损伤。
我们得出结论，aggNETs 在眼表炎症后阻塞 MG 导致 MGD。
