Lu Jing, Lu Fangfang, Peng Zhengwu, Zhang Zihe, Jiang Weijie, Meng Xia, Yi Xin, Chen Tuo, Fei Zhigang, Wang Yu, Yi Jiahuan, Deng Xujie, Zhang Jia, Wang Zhi, Xiao Qiguo
The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, Hunan, China.
Exp Eye Res. 2025 Feb;251:110204. doi: 10.1016/j.exer.2024.110204. Epub 2024 Dec 9.
Dry eye disease (DED) is a prevalent ophthalmic disease that affects millions of people worldwide. Iron overload and macrophage inflammation have been implicated in the development of murine DED, though the specific role of macrophages under iron overload conditions remains unclear. This study aimed to establish a novel iron overload-induced mouse model of DED and investigate macrophage involvement. The model was induced via intraperitoneal injection of D-glucoside iron. Results showed that macrophage depletion via clodronate liposomes (CL) significantly mitigated iron deposit, decreased ocular surface inflammation, improved tear production and restored the structure of ocular surface tissues. Furthermore, CL specifically targeted pro-inflammatory M1 macrophages and reduced levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α, effectively alleviating symptoms of DED. In conclusion, this study characterized a novel iron overload-induced DED mouse model and demenstrated that macrophage depletion mitigated the pathological changes in ocular surface and lacrimal gland tissues caused by iron overload, suggesting potential therapeutic strategies for further investigation in the treatment of DED.
干眼症（DED）是一种普遍的眼科疾病，影响着全球数百万人。铁过载和巨噬细胞炎症与小鼠干眼症的发展有关，尽管铁过载条件下巨噬细胞的具体作用仍不清楚。本研究旨在建立一种新型的铁过载诱导的小鼠干眼症模型，并研究巨噬细胞的参与情况。该模型通过腹腔注射D-葡萄糖苷铁诱导。结果表明，通过氯膦酸盐脂质体（CL）清除巨噬细胞可显著减轻铁沉积，减少眼表炎症，改善泪液分泌并恢复眼表组织的结构。此外，CL特异性靶向促炎性M1巨噬细胞并降低炎性细胞因子IL-1β、IL-6和TNF-α的水平，有效缓解干眼症症状。总之，本研究对一种新型的铁过载诱导的干眼症小鼠模型进行了表征，并证明巨噬细胞清除减轻了铁过载引起的眼表和泪腺组织的病理变化，为干眼症治疗的进一步研究提供了潜在的治疗策略。
