Our proposal builds upon preliminary data from robust published studies conducted by our research group involving adult mice exposed to powerful vesicants, such as lewisite (LEW) and nitrogen mustard (NM). We were among the first to recognize the detrimental effects of these agents on retinal health, which prompted us to investigate the molecular mechanisms underlying ocular and retinal tissue deterioration upon direct ocular exposure (DOE) to vesicants. While several research groups, including ours, are actively investigating potential molecular drivers of ocular tissue damage in adults, there is currently a lack of understanding of how vesicant exposure impacts the most vulnerable segments of our society, such as infants, juveniles, pregnant females, and the elderly. In this proposal, we aim to test the hypothesis that children are more susceptible to the same dose of DOE than adults due to the small size of the former’s eye globes and the differences in metabolic rates of ocular tissues. We will explore the mechanisms behind this increased vulnerability in children and propose a comparative study between DOEs in postnatal and adult mice. Two vesicants are proposed for this study. First, we plan to determine whether postnatal day (p) 20 C57BL6 mouse pups are more susceptible than adult mice to DOE to phenylarsine oxide (PAO), a known and validated surrogate of LEW. Second, we intend to research whether p20 C57BL6 mouse pups are more susceptible to DOE to NM than adult mice. Finally, we will investigate the key molecular signaling that is reprogramed upon postnatal DOE to PAO and NM compared to adult DOE. These data will provide evidence that DOE to vesicants is toxic for children and will identify them as the most vulnerable segment of exposed populations. This research will also validate p20 pups as a pediatric eye research model to study DOE to vesicants and establish, for the first time, the cellular and molecular mechanisms responsible for vesicant-mediated ocular injury. Additionally, this study will generate a therapeutic platform to overcome current technical difficulties in testing chemical warfare agents (CWA) for pediatric ophthalmic research and validate newly designed medical countermeasures (MCM).