Antioxidant Eye Wash Formulations to Counter Ocular Chemical Threats

NIH RePORTER · NIH · R21 · $194,438 · view on reporter.nih.gov ↗

Abstract

Abstract The Department of Homeland Security (DHS) lists over 300 “chemicals of concern.” These chemicals relate to the Chemical Facilities Anti-Terrorism Standard (CFATS). The chemicals on this list were provided by the U.S. Environmental Protection Agency (EPA), the international Chemical Weapons Convention, and the Department of Transportation (DOT). A large number of the chemicals on the DHS list are strong oxidizers. Since the eye is exposed and vulnerable to irreversible damage by strong oxidizers, which may permanently damage the eye or even cause loss of vision, developing a countermeasure for accidental or malicious ocular exposure to strong oxidizers is a high priority. The goal of the proposed research is to develop an eye wash solution containing antioxidants to mitigate damage to the eye caused by strongly oxidative chemical threats. To preliminarily test the hypothesis that damage induced by oxidative chemicals can be mitigated by a higher than physiological concentration of a tear antioxidant, we added a tear antioxidant to a 30-minute eye wash protocol as a treatment for ocular exposure to the strong oxidant chemical hypochlorite. Exposure of the eye to 8.25% hypochlorite followed by washing with saline alone resulted in significant loss of viable cells. However, when an antioxidant was added to the saline wash solution at 10× its physiological human tear concentration, eye damage was markedly reduced. The specific aims will answer the following questions: What is the optimal eye wash protocol and antioxidant concentration that will mitigate damage? Can preliminary results be further supported and the mechanism(s) of action better understood by the analysis of additional biochemical measurements including cell death and lipid and protein oxidation? Is the loss of viability induced by at least three other strong oxidant chemicals on the Department of Homeland Security (DHS)’s list of chemicals of concern also mitigated by washing with an antioxidant formulation? To answer these questions, the specific aims will rigorously test the hypothesis that postexposure washing with antioxidants can reduce loss of viability to the cornea. We will also test the hypothesis that the antioxidant directly decreases oxidation induced by oxidative corrosives before they damage a large percentage of the stroma using representative lipid and protein oxidation assays; if there is no clear relationship between the antioxidant and a reduction in lipid and protein oxidation, alternative cell- based studies will be used to evaluate the effects of the antioxidant on cell growth and differentiation in this context. We will also test the hypothesis that the mitigation of damage by the antioxidant is generalizable to other oxidants. We anticipate that the following outcomes will be achieved: 1) The unequivocal demonstration of less loss of viability of the cornea from levels that corrode to levels that are fully reversible within 21 days by washing with a solu...

Key facts

NIH application ID
10865074
Project number
5R21EY033713-02
Recipient
LEBRUN LABS, LLC
Principal Investigator
Stewart Lebrun
Activity code
R21
Funding institute
NIH
Fiscal year
2024
Award amount
$194,438
Award type
5
Project period
2023-07-01 → 2026-06-30