15 February 2013 Discovery of photochemical damage mechanisms using in vitro and in silico models
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Abstract
A computer-based model has been built that simulates the response of the retinal pigmented epithelial (RPE) cell to laser exposure in the photochemical (non-thermal) damage exposure range (≥ 100 s exposures). The modeling approach used is knowledge-based, modular, and hierarchical, allowing the explicit modeling of the cascades of intracellular events in response to laser application. Thus, the model can be used to both analyze existing in vitro data sets, as well as efficiently direct sampling strategies for future in vitro and in vivo studies. This model has been validated using laboratory data from several studies reported in the literature using blue light (413 nm and 458 nm) lasers with 100 s, 200 s, and 3600 s exposure durations. The model was able to predict the in vitro ED50 response curve from these studies, as well as the results for which we have no in vitro data (extrapolated based on irradiance reciprocity), within 1-6% for the shorter duration exposures. Based on exploration of this computer model using lethal vs. non-lethal laser exposure scenarios, the RPE cell’s oxidative stress response differs quantitatively very little with respect to typical oxidative stress sources such as superoxide and hydrogen peroxide. However, in the lethal exposure scenarios the model points to a potential tipping point in the oxidative stress response of the mitochondrial-based cellular energetics. Further studies are underway to explore issues related to the levels of ATP/ADP and GSH/GSSG that are predicted by the model in these lethal vs. non-lethal exposure scenarios.
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Pamela K. Fink, Pamela K. Fink, Michael L. Denton, Michael L. Denton, Cherry C. Castellanos, Cherry C. Castellanos, Amanda J. Tijerina, Amanda J. Tijerina, Kurt J. Schuster, Kurt J. Schuster, Jeffrey W. Oliver, Jeffrey W. Oliver, "Discovery of photochemical damage mechanisms using in vitro and in silico models", Proc. SPIE 8579, Optical Interactions with Tissue and Cells XXIV, 85790A (15 February 2013); doi: 10.1117/12.2017669; https://doi.org/10.1117/12.2017669
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