Clodronate liposome-mediated macrophage depletion ameliorates iron overload-induced dry eye disease.

Abstract

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.