Pupillary light response in guinea pigs and swine exposed to organophosphate agents (1143.5)

Abstract

Here we report a study to more precisely define and quantify the relationship between organophosphate agent exposure, including pesticides and nerve agents, with cholinesterase inhibition and the ocular biomarkers that are induced. A thorough investigation of these relationships was conducted to subsequently refine pupillary algorithms for the automated detection of organophosphate exposures with greater specificity regarding level of exposure, the extent of cholinesterase inhibition, and the temporal presentation and persistence of the ocular biomarkers. A guinea pig model was exposed to varying concentrations of parathion (pesticide), soman and VX (nerve agents) to methodically detail both the temporal and quantitative occurrence of pupillary deficits (anticholinesterase biomarkers) to determine the most sensitive, accurate diagnostic algorithms in these animal models. Dose‐response curves and temporal‐response curves for both pupillary deficits and generalized symptoms were developed for each agent used. Based upon previous studies dose ranges were conducted from the LD50 to 3000‐fold below the LD50 to incorporate lethal and sub‐lethal exposures without decreasing the potential sensitivity of the ocular biomarkers. In addition, cholinesterase assays were performed at various time points post‐exposure. The key finding of this study was that after exposure to organophosphates changes in pupillary response were detected prior to changes in acetylcholine esterase levels in guinea pigs. This opens the possibility of early detection to organophosphate exposure in a non‐invasive manner that does not require the use of enzyme markers. We are in the process of duplicating these studies in swine and swine data will be presented.Grant Funding Source: Supported by Defense Threat Reduction Agency