A physiologically based model to capture species-dependent differences in oxygen distribution in the posterior eye
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German C, Boyer A, Przekwas A, El Bader S, Cabal A. A physiologically based model to capture species-dependent differences in oxygen distribution in the posterior eye. MAIO [Internet]. 2021 Sep. 17 [cited 2021 Oct. 24];3(1):10-42. Available from: https://www.maio-journal.com/index.php/MAIO/article/view/111

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Copyright (c) 2021 Carrie German, Alex Boyer, Andrzej Przekwas, Suzy El Bader, Antonio Cabal

Keywords

computational modeling; physiologically based modeling; posterior eye; oxygen; translational tool

Abstract

Ocular barriers to drug transport make delivery of effective doses to posterior targets exceptionally difficult. Animal models have commonly been used to evaluate drug distribution and penetrability, but translational tools to determine human dosing are lacking. Here we present a framework for modeling interspecies variation by simulating oxygen distribution in the posterior eye, from outer vitreous to the sclera. Posterior eye models of mouse, rabbit, and human are presented with modifications based solely on species-dependent anatomical and physiological differences. The model includes tissue and vascular contributions to transport. In addition to oxygen, nitric oxide and its impact on oxygen metabolism is simulated. Depth-dependent retinal oxygen partial pressure profiles are in good agreement with experimental data for all three species. The model can be further extended to evaluate the variations of retinal oxygenation in response to various drugs, formulations, administration protocols, and treatment plans. Further, this framework of ocular physiologically based pharmacokinetic/pharmacodynamic models could support animal to human translation, a critical step in the drug development process.

https://doi.org/10.35119/maio.v3i1.111
111 PDF

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