Antiferromagnetic Dimanganese Catalase Mimics: Targeting Oxidative Stress to Mitigate Corneal Neovascularization Post-alkali Injury

作者：Hang Zhang, Kan Xu, Jiahui Wu, Dijie Qiao, Xiangyu Tan, Rong Sun, Bingwu Wang, Xi-Long Leng, Ke Wang, Hao‐Ling Sun, Song Gao, Wei Chi, Jun‐Long Zhang · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c08110 · 被引用次数：11 · 研究领域：Advanced Nanomaterials in Catalysis、Advanced Glycation End Products research、Corneal Surgery and Treatments

Corneal alkali-burn injury is a common ophthalmic emergency that elevates oxidative stress in the ocular microenvironment, leading to cellular apoptosis and corneal neovascularization. To address this challenge, we report a binuclear manganese complex ( Mn-2 ) featuring a catalase-mimetic antiferromagnetic Mn–O–Mn core, which efficiently scavenges hydrogen peroxide, a key contributor to oxidative damage. This structure enables effective hydrogen peroxide scavenging while concurrently suppressing the Fenton reaction, a major driver of oxidative injury. In comparison to a mononuclear manganese complex (MnSalen, Mn-1 ) and a tri-MnSalen cryptand complex ( Mn-3 ), Mn-2 demonstrated significantly enhanced cytoprotection in human corneal epithelial cells (HCECs). Mechanistic studies revealed that Mn-2 modulates the expression of antioxidant-related proteins, including NQO1 and catalase, as well as both pro- and antiapoptotic proteins such ascleaved caspase 3, cytochrome c, and Bcl-2. In murine models of alkali-burn, topical administration of Mn-2 effectively reduced pathological corneal damage, alleviating corneal inflammatory edema, opacity, and neovascularization, to levels comparable to those achieved with clinically available dexamethasone. Importantly, the eye drops containing Mn-2 exhibited minimal ocular surface toxicity, highlighting their safety for therapeutic use. These findings position Mn-2 as a promising therapeutic option for vision-threatening corneal injuries, ther...