Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA; Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Exp Eye Res. 2023 Aug;233:109565. doi: 10.1016/j.exer.2023.109565. Epub 2023 Jul 3.
Mustard agents are vesicants that were used in warfare multiple times. They are potent alkylating agents that activate cellular pathways of apoptosis, increase oxidative stress, and induce inflammation. Eyes are particularly susceptible to mustard exposure with a wide range of ocular surface damage. Three main categories of mustard-related eye injuries are acute, chronic, and delayed-onset manifestations. Mustard keratopathy (MK) is a known complication characterized by corneal opacification, ulceration, thinning, and neovascularization that can lead to severe vision loss and discomfort. Recently, a few reports demonstrated the role of senescence induction as a new pathological mechanism in mustard-related injuries that could affect wound healing. We ran the first murine model of delayed-onset MK and nitrogen mustard-induced senescence, evaluating the pathological signs of senescence in the cornea using beta-galactosidase staining. Our results suggest that nitrogen mustard exposure causes senescence in the corneal cells, which could be the underlying mechanism for chronic and late-onset ocular surface damage. We also found a significant correlation between the percentage of positive beta-galactosidase staining and the degree of fibrosis in the cornea. This provides valuable insight into the possible role of anti-senescence drugs in the near future for accelerating corneal healing and restricting fibrosis in patients with mustard keratopathy.
芥子气是一种曾多次在战争中使用的糜烂性毒剂。它是一种有效的烷化剂，能激活细胞凋亡途径，增加氧化应激，并诱导炎症。眼睛特别容易受到芥子气暴露的影响，导致广泛的眼表损伤。芥子气相关眼部损伤主要有急性、慢性和迟发性三种表现。芥子气角膜病变（MK）是一种已知的并发症，其特征为角膜混浊、溃疡、变薄和新生血管形成，可导致严重的视力丧失和不适。最近，有一些报道表明衰老诱导是芥子气相关损伤的一种新的病理机制，可能影响伤口愈合。我们建立了首例迟发性 MK 和氮芥诱导衰老的小鼠模型，使用β-半乳糖苷酶染色评估角膜中衰老的病理标志。我们的结果表明，氮芥暴露会导致角膜细胞衰老，这可能是慢性和迟发性眼表损伤的潜在机制。我们还发现β-半乳糖苷酶染色阳性细胞的百分比与角膜纤维化的程度之间存在显著相关性。这为未来抗衰老药物在加速角膜愈合和限制 MK 患者纤维化方面的可能作用提供了有价值的见解。
