Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study
A) Total number of stalk cells vs. time. B) Total number of stalk cells confined in the sub-RPE space vs. time. C) Total number of stalk cells in contact with the POS (stalk cells in the sub-retinal space) vs. time. D) Total number of RPE cells vs. time. E) Total contact area between RPE cells and BrM vs. time. F) Total contact area between POS cells and BrM vs. time. The different colors represent the results of 10 simulation replica of the adhesion scenario (RRl = 1, RRp = 3, RBl = 1, RBp = 2, ROl = 3) (Table S7, adhesion scenario ID: 83). CNV initiates in all replicas and all develop ET1 CNV. A few stalk cells in most replicas die due to lack of RPE-derived VEGF-A. (C) Stalk cells cross the RPE and invade the sub-retinal space once the number of stalk cells in the sub-RPE space reaches ∼60 cells, which usually occurs within first two months after initiation. CNV progression to the sub-retinal space is complete around month 5. (D) The RPE remains viable in all replicas. (E) The contact area between the RPE and BrM decreases as ET1 CNV develops, and remains constant afterwards throughout LT3 CNV. (F) The POS contacts BrM a few times, but the contact area and duration are both small, so the RPE does not develop any persistent or substantial holes.