Chen Yi-Zhou, Chen Zhi-Yu, Tang Yu-Jun, Tsai Cheng-Han, Chuang Yu-Lun, Hsieh Erh-Hsuan, Tucker Lachlan, Lin I-Chan, Tseng Ching-Li
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei City 11031, Taiwan.
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia.
Pharmaceutics. 2021 Oct 27;13(11):1801. doi: 10.3390/pharmaceutics13111801.
Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of <5 μM lutein (L5) and <1% PVA (P1) maintained the cell viability at 80%. A real-time PCR showed that the inflamed human corneal epithelial cells (HCECs) cocultured with L5P1 had downregulated expression of inflammatory genes such as IL-1β, IL-6, and TNF-α. In a benzalkonium chloride- (BAC) induced DES mouse model, AT/L5P1 could repair damaged corneas, elevate tear secretion, increase the number of goblet cells, and inhibit the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in the cornea. In conclusion, we demonstrate that lutein/PVA as eye drops could prolong the drug ocular retention time and effectively to decrease inflammation in DES mice. Therefore, lutein, obtained from eye drops, has a potential therapeutic role for DES.
干眼症（DES）是一种常见的眼科疾病，它会减少泪液分泌，导致眼睛干涩、畏光、疼痛、严重的角膜破裂甚至失明。眼和泪腺炎症是DES的病理机制之一。因此，有效抑制炎症是治疗DES的关键策略。叶黄素常见于健康食品中，在角膜或视网膜相关细胞中具有抗炎作用，可能是治疗DES的一种潜在疗法。本研究在小鼠模型中研究了将叶黄素添加到人工泪液（AT）中作为治疗DES的滴眼剂配方。聚乙烯醇（PVA）用作增稠剂以增加滴眼剂的粘度，从而延长药物在眼表的滞留时间。在人角膜上皮细胞（HCE-2）中进行的WST-8试验表明，浓度<5μM的叶黄素（L5）和<1%的PVA（P1）可使细胞活力维持在80%。实时PCR显示，与L5P1共培养的炎症人角膜上皮细胞（HCECs）中，白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）等炎症基因的表达下调。在苯扎氯铵（BAC）诱导的DES小鼠模型中，AT/L5P1可修复受损角膜，提高泪液分泌，增加杯状细胞数量，并抑制角膜中IL-1β、IL-6和TNF-α等炎症细胞因子的产生。总之，我们证明叶黄素/PVA滴眼剂可延长药物在眼部的滞留时间，并有效减轻DES小鼠的炎症。因此，从滴眼剂中获得的叶黄素对DES具有潜在的治疗作用。
