Abstract
Purpose :
Retinal vascular development is dependent on diffusible chemical morphogens (ie vascular endothelial growth factor (VEGF)) which promotes vessel growth in a characteristic branching fashion; others have argued it follows a previously described pattern known as diffusion-limited aggregation (DLA). In this novel description, we propose that the fovea developmentally has an anti-vascular growth effect, whether by diffusible morphogen or otherwise, which may repel vasculogenesis. We use a computational simulation to illustrate the morphologic features this simple modification of typical DLA explains in retinal vascular development.
Methods :
A computational model simulating diffusion limited aggregation was written in Python 3.10 in the Anaconda scientific environment. A square lattice was coded where the retinal tissue was simulated to be a circle of radius 200 grid points. An optic disc was simulated as an initial seed point, and particles (ie VEGF) were released from the grid, after which these particles underwent Brownian motion until they aggregated with the seed particle, or another aggregated particle. We simulated that this growing network of aggregated particles "perfused" the surround 10 grid points, meaning they would no longer release VEGF particles. Finally, a "fovea" was simulated as a central point on the grid which would repel the diffusing particles by the inverse square law.
Results :
A representative sample of the progression of this simulation is shown in the model. We demonstrate that simply supposing that the fovea has a repulsive effect on the chemical morphogens that drive retinal vascular growth (ie VEGF). This may explain 1) the architecture of the foveal avascular zone, 2) the reason foveate mammals tend to have 4 arcades, whereas non-foveate animals tend to have 6-8 arcades, 3) the physiology of the “notch” that sometimes develops in retinopathy of prematurity in the temporal macula.
Conclusions :
Disparate morphologic features of retinal vascular development could be explained simply by an inferred foveal repulsive effect during development. This may have implications on aberrations in foveal development, for example as seen in ROP, and motivate investigation to the cause of this effect. Additionally, foveal hypoplasia may be in part caused by imbalance between VEGF and the repulsive compound.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.