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 replicas of the adhesion scenario (RRl = 3, RRp = 3, RBl = 1, RBp = 1, ROl = 1) (Table S6 adhesion scenario ID: 93). (A, B) CNV initiates in all replicas. By 3 months, most replicas form a developed sub-RPE capillary network composed of ∼20 to 40 stalk cells (∼1500 to 3000 cells/mm2). 8 replicas develop Early Type 1 (ET1) CNV. Only one replica shows Stable Type 1 (S11) CNV. Some stalk cells in most replicas die due to lack of RPE-derived VEGF-A. (C) Two replicas show Stable Type 2 (S22) CNV (Early (ET2) and Late Type 2 (LT2) CNV, black and dark red lines). 7 replicas show LT2 CNV. (D) The RPE remains viable in all replicas. (E) The contact area between the RPE and BrM decreases as either ET1 CNV or S11 CNV develops, and remains constant during ET2 CNV. RPE reattaches to BrM during T12 CNV. (F) The POS contacts BrM once, but the contacts area and duration are both small, so the RPE does not develop any persistent or substantial holes.