Kahale Francesca, Surico Pier Luigi, Singh Rohan Bir, Dashti Parisa, Hazra Swatilekha, Bhullar Shilpy, Yin Jia, Chen Yihe, Dana Reza
Laboratory of Ocular Immunology, Transplantation and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Laboratory of Ocular Immunology, Transplantation and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Exp Eye Res. 2025 Sep;258:110515. doi: 10.1016/j.exer.2025.110515. Epub 2025 Jul 8.
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.
接触氮芥（NM）会导致严重的角膜损伤，引发持续性角膜炎症、上皮损伤、内皮功能障碍和视力损害。减轻这些影响的有效治疗策略仍然有限。本研究评估了α-黑素细胞刺激素（α-MSH）在NM诱导的小鼠角膜损伤模型中的保护作用。将C57BL/6小鼠暴露于NM，并全身给予α-MSH治疗28天。进行临床评估、组织学分析、眼前节光学相干断层扫描（AS-OCT）和免疫组织化学，以评估角膜完整性、炎症和细胞存活情况。与未治疗的对照组相比，α-MSH治疗显著减轻了角膜上皮病变，防止了上皮变薄，并保留了角膜缘上皮细胞密度。α-MSH治疗的小鼠中央基质厚度显著降低，表明角膜水肿减轻。内皮细胞形态得以保留，治疗小鼠的内皮细胞密度更高、变异系数降低且六角形化改善。TUNEL检测显示，在α-MSH治疗的眼睛中，早期（第7天）和晚期（第28天）中央和角膜缘角膜区域的凋亡均显著减少。这些发现突出了α-MSH的细胞保护和抗炎作用。通过减轻NM诱导的损伤，α-MSH保留了角膜的结构完整性和功能，证明了其作为芥子气角膜病变治疗干预措施的潜力。
