title: Prediction of passive drug permeability across the blood-retinal barrier.
abstract: OBJECTIVE
  The purpose of this study is to develop a computational model of the physical barrier function of the outer blood-retinal barrier (BRB), which is vital for normal retinal function. To our best knowledge no comprehensive models of BRB has been reported.
  
  
  METHODS
  The model construction is based on the three-layered structure of the BRB: retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris endothelium. Their permeabilities were calculated based on the physical theories and experimental material and permeability studies in the literature, which were used to describe diffusional hindrance in specific environments.
  
  
  RESULTS
  Our compartmental BRB model predicts permeabilities with magnitudes similar to the experimental values in the literature. However, due to the small number and varying experimental conditions there is a large variability in the available experimental data, rendering validation of the model difficult. The model suggests that the paracellular pathway of the RPE largely defines the total BRB permeability.
  
  
  CONCLUSIONS
  Our model is the first BRB model of its level and combines the present knowledge of the BRB barrier function. Furthermore, the model forms a platform for the future model development to be used for the design of new drugs and drug administration systems.
authors.affiliation: BioMediTech, Tampere University of Technology, Tampere, Finland, aapo.tervonen@tut.fi.
authors.forename: Aapo
authors.initials: A
authors.lastname: Tervonen
authors.forename: Iina
authors.initials: I
authors.lastname: Vainio
authors.forename: Soile
authors.initials: S
authors.lastname: Nymark
authors.forename: Jari
authors.initials: J
authors.lastname: Hyttinen
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000033:anatomy & histology / Q000378:metabolism*; D002417:Cattle; D003198:Computer Simulation; D004058:Diffusion; D006801:Humans; D008954:Models, Biological; D010539:Permeability; D010599:Pharmacokinetics; D013552:Swine