Therapeutic Potential of Combined 5% Lifitegrast and Tocopherol Eye Drops in Managing Inflammation and Oxidative Stress in Murine Dry Eye.

IF 4.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pharmaceuticals Pub Date : 2025-01-01 DOI:10.3390/ph18010038
Jayoung Moon, Enying Jiang, Jingting Liu, Hui Jin, Hee Su Yoon, Hoon-In Choi, Ji Suk Choi, Hong Qi, Hyeon-Jeong Yoon, Kyung Chul Yoon
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Abstract

Background/Objectives: This study aimed to evaluate the therapeutic effects of combined 5% lifitegrast (LF) and tocopherol (TCP) eye drops in a murine experimental dry eye (EDE) model. Methods: Female C57BL/6 were divided into seven groups: untreated controls, EDE control, EDE + 0.05% cyclosporin A (CsA), EDE + tocopherol (TCP), EDE + 5% LF, EDE + 5% LF + TCP (once daily), and EDE + 5% LF + TCP (twice daily). Clinical parameters (tear volume, tear break-up time (TBUT), corneal fluorescein staining score (CFSS), tear film lipid layer grade (TFLLG)) were assessed on days 7 and 14. Goblet cell density in the conjunctiva, CD4+ IFN-γ+ T cells, interleukin levels, reactive oxygen species (ROS) levels, and corneal apoptotic cells were analyzed on day 14. Results: Monotherapy with 0.05% CsA and LF showed improvements in all clinical parameters compared to the EDE control (p < 0.05). Combination therapy groups demonstrated superior improvements in clinical parameters compared to the EDE control, 0.05% CsA, and 5% LF groups. CD4+ IFN-γ+ T cell percentages and ROS levels in the cornea and conjunctiva were markedly reduced in the combination groups compared with the 0.05% CsA and 5% LF groups (p < 0.01). Furthermore, corneal apoptotic cells significantly decreased in the combination groups compared to the 0.05% CsA and TCP groups (p < 0.05). Conclusions: Combined 5% LF and TCP eye drops improved tear film parameters and reduced inflammatory and oxidative stress markers. The combination therapy can mitigate ocular surface damage by managing inflammation and oxidative stress in dry eye.

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5%立替格斯特和生育酚联合滴眼液治疗小鼠干眼症炎症和氧化应激的潜力。
背景/目的:本研究旨在评价5%立替格司特(LF)和生育酚(TCP)联合滴眼液对小鼠实验性干眼(EDE)模型的治疗作用。方法:将女性C57BL/6分为7组:未治疗对照组、EDE对照组、EDE + 0.05%环孢素A (CsA)、EDE +生育酚(TCP)、EDE + 5% LF、EDE + 5% LF + TCP(每日1次)、EDE + 5% LF + TCP(每日2次)。于第7天和第14天评估临床参数(泪液体积、泪液破裂时间(TBUT)、角膜荧光素染色评分(CFSS)、泪液膜脂质层分级(TFLLG))。观察第14天结膜杯状细胞密度、CD4+ IFN-γ+ T细胞、白细胞介素水平、活性氧(ROS)水平和角膜凋亡细胞。结果:与EDE对照组相比,0.05% CsA和LF单药治疗在所有临床参数上均有改善(p < 0.05)。与EDE对照组、0.05% CsA组和5% LF组相比,联合治疗组在临床参数方面表现出更好的改善。与0.05% CsA和5% LF组相比,联合用药组角膜和结膜内CD4+ IFN-γ+ T细胞百分比和ROS水平均显著降低(p < 0.01)。此外,与0.05% CsA和TCP组相比,联合组角膜凋亡细胞明显减少(p < 0.05)。结论:5% LF和TCP联合滴眼液可改善泪膜参数,降低炎症和氧化应激指标。联合治疗可通过控制干眼炎症和氧化应激减轻眼表损伤。
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来源期刊
Pharmaceuticals
Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍: Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.
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