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P. K. Fink, M. L. Denton, L. Ibekwe, S. Ryan, X. Zhu, J. Oliver, G. Pocock; Computational Modeling of Multiple Concurrent Oxidative Stress Processes in the Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1411.
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A computer-based model was developed for various oxidative stress processes on the retina. The model allows for the exploration in silico of questions concerning the subcellular processes in RPE when exposed to triggers of oxidative stress, such as lasers and aging.
The computer-based model was developed using a technique known as BioFusion, that involves a specific process of collecting, analyzing, documenting, and organizing knowledge available in the area of interest and then using this knowledge to build a model. Implementation of the model is in a commercial, off-the-shelf modeling tool that runs on a standard PC. This modeling technique was developed specifically for building large, complex models of biological processes and systems. The modeling approach is hierarchical and modular to deal with the complexity of the processes. Also, it is capable of modeling the RPE cell in an in vitro or an in vivo configuration.
We have collected a large repository of information relating RPE cellular responses to photo-oxidative stresses based on peer-reviewed articles and other sources. We tested the ability of the model to indicate damage in the RPE upon simulation of laser exposures of various wavelength and exposure duration. We followed key intracellular processes in the RPE cell in response to laser irradiation (metabolism, oxygen consumption, lipid peroxidation, protein damage, GSSH metabolism, RedOx enzymes, iron and the Fenton reaction, lipofuscin production) We analyzed the effects of melanin, NO, Vitamin A, and heat shock proteins on the cellular response to laser exposure.
The model is capable of responding to acute oxidative insults such as laser exposure, as well as to slower insults such as low-level light exposure over extended durations. The model allowed for interactive exploration of questions and theories that would be difficult if not impossible to explore in vitro or in vivo alone.
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