Treatment of nitrogen mustard-induced corneal injury with alpha-melanocyte stimulating hormone

Abstract

Nitrogen mustard (NM) exposure leads to severe corneal damage, resulting in persistent corneal inflammation, epithelial damage, endothelial dysfunction, and vision impairment. Effective therapeutic strategies to mitigate these effects remain limited. This study evaluates the protective effects of alpha-melanocyte-stimulating hormone (α-MSH) in a murine model of NM-induced corneal injury. C57BL/6 mice were exposed to NM and treated with systemic α-MSH for 28 days. Clinical assessments, histological analysis, anterior segment optical coherence tomography (AS-OCT), and immunohistochemistry were performed to evaluate corneal integrity, inflammation, and cell survival. α-MSH treatment significantly reduced corneal epitheliopathy, prevented epithelial thinning, and preserved limbal epithelial cell density compared to untreated controls. Central stromal thickness was significantly lower in α-MSH-treated mice, suggesting reduced corneal edema. Endothelial cell morphology was preserved, with higher endothelial cell density, reduced coefficient of variation, and improved hexagonality in treated mice. TUNEL assay demonstrated significantly lower apoptosis in both central and limbal corneal regions at early (day 7) and late (day 28) time points in α-MSH-treated eyes. These findings highlight the cytoprotective and anti-inflammatory effects of α-MSH. By mitigating NM-induced injury, α-MSH preserves corneal structural integrity and function, demonstrating its potential as a therapeutic intervention for mustard gas keratopathy.