Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study
Our model includes two types of cell-cell and cell-BrM adhesion: 1) labile adhesion and 2) junctional adhesion. Modeled labile adhesion represents cell-cell or cell-ECM labile adhesion in the absence of strong junctional structures (e.g., RPE-POS adhesion). Junctional adhesion combines labile adhesion at cell boundaries with plastic coupling (e.g., between neighboring cells or between BrM and cells). Plastic coupling simulates cytoskeletally-coupled junctional structures as breakable springs (see the Methods section in supplementary Text S3) that mechanically connect neighboring cells and also connect cells to BrM. Junctional adhesion represents biological epithelial or endothelial junctional adhesion or cell-ECM focal adhesion. In the model, a single junctional adhesion between RPE cells and BrM represents the complex biological adhesion between RPE cells and their basal laminae (RBaL), adhesion between the basal laminae and their basement membrane (RBaM) and adhesion between RBaM and BrM (inset). Modeled adhesion processes are: EC-EC and EC-BrM junctional adhesion; EC-RPE, EC-POS and EC-PIS labile adhesion; RPE-RPE and RPE-BrM junctional adhesion; RPE-PIS and RPE-POS labile adhesion; PIS-PIS, PIS-POS and POS-POS junctional adhesion. Key: BrM: Bruch's membrane, RPE: retinal pigment epithelium, RBaM: basement membrane of the RPE, RBaL: basal lamina of the RPE, POS: photoreceptor outer segment, PIS: photoreceptor inner segment.