Antiferromagnetic Dimanganese Catalase Mimics: Targeting Oxidative Stress to Mitigate Corneal Neovascularization...

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, thereby addressing a critical gap in ocular regenerative medicine.