Retinal injury mouse model and pathophysiological assessment of the effect of arsenical vesicants. (January 2023)

• Record Type: Journal Article
• Authors: Zhylkibayev, Assylbek; Srivastava, Ritesh; Anantharam, Poojya; Crotch, Claire; Athar, Mohammad; Gorbatyuk, Marina
• Is Part Of: Experimental eye research. Volume 226(2023)
• Publication Date: 2023-01
• Subjects: Lewisite -- Phenylarsine oxide -- Corneal and retinal injury -- Mouse model -- Retinal degeneration; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.109354
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: 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. Highlights: The direct ocular exposure to arsenicals in mice causes severe retinal damage. Both the lewisite and PAO exposures activate the proinflammatory cytokine cascade and apoptotic cell death program. Mouse model of PAO-induced ocular toxicity allows to validate new medical countermeasures to treat retinal injury.