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Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

Figure 16

Dynamics of sub-retinal CNV to sub-RPE CNV progression (P23 CNV Progression).

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 = 1, RRp = 1, RBl = 1, RBp = 1, ROl = 1) (Table S9, adhesion scenario ID: 108). CNV initiates in all replicas and all develop ET2 CNV. A few stalk cells in most replicas die due to lack of RPE-derived VEGF-A. (B) Stalk cells cross the RPE and invade the sub-RPE space once the number of stalk cells in the sub-RPE space reaches ∼50 cells, which usually occurs during the first month after initiation. Stalk cells gradually invade the sub-RPE space during one simulated year. (D) Up to 30 RPE cells (30% of the total) die. The number of RPE cell deaths increases with the number of sub-RPE stalk cells. (E) The contact area between the RPE and BrM decreases as P23 CNV develops. (F) In all replicas the POS contacts BrM persistently and extensively, as the RPE develops substantial holes (see Figure 17).

Figure 16