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Antioxidant Eye Wash Formulations to Counter Ocular Chemical Threats

Award Number: R21EY033713
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Antioxidant Eye Wash Formulations to Counter Ocular Chemical Threats - 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 solution containing antioxidants after hypochlorite-induced damage. 2) Confirmation that the mechanism of action responsible for the reduced loss of viability is the inactivation of strong oxidants as they corrode ocular tissue with time, or, as determined by alternative strategies, that washing with antioxidants improves viability after strong oxidant exposure. 3) Demonstration that an antioxidant eye wash countermeasure can be used for other strong oxidants on the DHS list of chemicals of concern. These outcomes may establish that tear-related antioxidants at high concentrations can reduce eye damage caused by strong oxidizing chemicals on the DHS list of chemicals of concern. By demonstrating that high concentrations of naturally occurring tear antioxidants can mitigate eye damage, the proposed exploratory research will increase our understanding of the potential use of antioxidants to reduce eye damage after accidental exposure to or attack with strong oxidant chemicals. 1


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $194,438 )
2024	2024	LEBRUN LABS LLC	3301 E MIRALOMA AVE STE 194	ANAHEIM	CA	92806	ORANGE	USA	Vision Research	000	2	7/10/2024	NON-COMPETING CONTINUATION	$194,438
														Subtotal = $194,438

Issue Date FY: 2023 ( Subtotal = $165,000 )
2023	2023	LEBRUN LABS LLC	3301 E MIRALOMA AVE	ANAHEIM	CA	92806	ORANGE	USA	Vision Research	000	1	6/12/2023	NEW	$165,000
														Subtotal = $165,000

Grand Total All Awards = $359,438

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Antioxidant Eye Wash Formulations to Counter Ocular Chemical Threats

Award Number: R21EY033713

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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