Retinal injury mouse model and pathophysiological assessment of the effect of arsenical vesicants.

Retinal injury mouse model and pathophysiological assessment of the effect of arsenical vesicants.
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DOI:
10.1016/j.exer.2022.109354
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发表时间:
2023-01
影响因子:
3.4
通讯作者:
Gorbatyuk, Marina
Gorbatyuk, Marina
中科院分区:
医学3区
文献类型:
--
作者:
Zhylkibayev, Assylbek;Srivastava, Ritesh;Anantharam, Poojya;Crotch, Claire;Athar, Mohammad;Gorbatyuk, Marina

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眼睛对化学战剂的脆弱性是其他器官的十倍。一致地,暴露于起泡砷路易斯矿(LEW)会导致严重的角膜损伤,导致慢性炎症、角膜混浊、血管化和水肿,最终导致角膜细胞死亡。然而,尽管砷引起的眼前房发病机制的研究领域取得了进展,但砷暴露引起的视网膜损伤尚未确定。因此,我们研究了直接眼部暴露 (DOE) LEW 和苯胂氧化物 (PAO) 对视网膜的影响。在 MRIGlobal 设施中使用气帽法对砷进行 DOE 分析,或者在 UAB 中使用浸泡在不同 PAO 浓度溶液中的眼罩进行分析。在暴露后 1、3、14 和 28 天对动物进行评估。研究结果表明,这两种砷都会导致严重的视网膜损伤,激活促炎程序并引发细胞凋亡。此外,DOE 对 PAO 导致 ERG 振幅以剂量依赖性方式减小,表明存在严重的视网膜损伤。目前的研究建立了砷诱发眼损伤的原型小鼠模型,可广泛用于识别视网膜损伤病理学中涉及的关键细胞信号通路,并验证针对眼损伤进展的医学对策。
The eye is ten times more vulnerable to chemical warfare agents than other organs. Consistently, exposure to vesicant arsenical lewisite (LEW) manifests significant corneal damage leading to chronic inflammation, corneal opacity, vascularization, and edema, culminating in corneal cell death. However, despite the progress has made in the research field investigating arsenical-induced pathogenesis of the anterior chamber of the eye, the retinal damage resulted from exposure to arsenicals has not been identified yet. Therefore, we investigated the effects of direct ocular exposure (DOE) to LEW and phenylarsine oxide (PAO) on the retina. DOE to arsenicals was conducted using the vapor cap method at the MRIGlobal facility or an eye patch soaked in solutions with different PAO concentrations at UAB. Animals were assessed at 1, 3, 14, and 28 days postexposure. Results of the study demonstrated that both arsenicals cause severe retinal damage, activating proinflammatory programs and launching apoptotic cell death. Moreover, the DOE to PAO resulted in diminishing ERG amplitudes in a dose-dependent manner, indicating severe retinal damage. The current study established a prototype mouse model of arsenical-induced ocular damage that can be widely used to identify the key cellular signaling pathways involved in retinal damage pathobiology and to validate medical countermeasures against the progression of ocular damage.
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