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

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 (<b>Mn-2</b>) 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, <b>Mn-1</b>) and a tri-MnSalen cryptand complex (<b>Mn-3</b>), <b>Mn-2</b> demonstrated significantly enhanced cytoprotection in human corneal epithelial cells (HCECs). Mechanistic studies revealed that <b>Mn-2</b> 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 <b>Mn-2</b> 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 <b>Mn-2</b> exhibited minimal ocular surface toxicity, highlighting their safety for therapeutic use. These findings position <b>Mn-2</b> as a promising therapeutic option for vision-threatening corneal injuries, thereby addressing a critical gap in ocular regenerative medicine.