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

Figure 17

Snapshots of a simulation replica exhibiting sub-retinal CNV to sub-RPE CNV progression (P23 CNV).

3D and 2D visualization of a simulation replica forming P23 CNV in one simulated year (RRl = 1, RRp = 1, RBl = 1, RBp = 1, ROl = 1) (adhesion scenario ID: 108, simulation ID: 1080). Snapshots of the simulation at months 1 (A), 3 (B), 6 (C) and 12 (D). (A2-D2) Cross-sections of (A1-D1) parallel and adjacent to BrM, so stalk cells shown in (A2-D2) contact BrM. The black open circles (A1-2) at the top corner and outline back arrows (A1-2) at the location of the hole in BrM are guides to the eye to align A2 to A1. The alignment is consistent across all panels. (A) Stalk cells (solid black arrow) invade the sub-retinal space through the hole in BrM (A1-2, black outline arrows) that the tip cell form during the first 24 hours of the simulation and form a fully developed sub-retinal capillary network by month 1. (A2) Only a few stalk cells, mostly near the hole in BrM, invade the sub-RPE space during the first month. (B1, C1) The sub-retinal capillary network does not grow significantly. (B2, C2) Additional stalk cells invade the sub-RPE space. (D) More stalk cells invade the sub-RPE space, disrupting the RPE and causing a micro-tear (D1-2, black arrows). The POS contacts BrM at the location of the RPE tear. Cell type colors: 1) POS and PIS: light purple, 2) RPE: brown (stalk cells in the sub-retinal space have lighter shading), 3) Stalk cells: green (3D-visualized stalk cells in the sub-retinal space have lighter shading), 4) Vascular cells (CC): red, 5) BrM: light blue. Scale bars ∼50 µm. We have rendered the boundaries of individual cells in A1-D1 as semi-transparent membranes. POS, PIS and RPE cells are rendered more transparent to show the underlying structures. See also Video S5.

Figure 17

doi: https://doi.org/10.1371/journal.pcbi.1002440.g017