Computational Model of Passive Diffusion Across the Retinal Pigment Epithelium

Abstract

Retinal pigment epithelium (RPE) is an important part of the normal visual function. Located behind the retina, one of its main functions as a part of the blood-retinal barrier is to regulate the transport between the retina and systemic blood circulation. The barrier properties, and changes in them, have a role in certain retinal diseases, such as age-related macular degeneration. Previously, mostly pharmacokinetic compartmental models have been proposed. In this study, for the first time we introduce an accurate physical structure-based model of passive diffusion across the RPE.Our model relates the permeability coefficients of RPE structures to the physicochemical properties of materials forming the RPE. Model is based on a similar corneal diffusion model proposed by Edwards & Prausnitz (2001). Transcellular and paracellular diffusion components are described by separate permeability equations based on the material properties of each pathway and the basic interactions between each pathway and the characteristics of the diffusing molecule. The structure of our tight junction (TJ) model has not been utilized in other structure-based epithelial models of this type, and it takes into account both the pore pathway for small molecules and the leak pathway for large molecules.Our RPE model was able to predict correct magnitude for the permeabilities and its behavior corresponds to experimental results. Further, the permeability magnitude and behavior of the TJ model appear similar to the experimental data from intestine epithelial cell TJs. However, due to the inconsistent experimental data of RPE permeability, rigorous validation cannot be made.RPE barrier models would facilitate novel drug development against retinal diseases. Our model forms a good platform for the future development and refinements as it combines our knowledge of the RPE structure and diffusion.