Abstract
Purpose :
Exudative age-related macular degeneration (AMD), characterized by neovascularization in the retina, begins when retinal pigment epithelial (RPE) cells secrete excess amounts of angiogenic factors. Varying concentrations of pro-angiogenic vascular endothelial growth factor (VEGF) and pigment epithelial derived factor (PEDF), an antiangiogenic factor, affect the growth of neovessels. Computational modeling provides further insights into blood vessel growth involving VEGF and PEDF concentrations.
Methods :
A two-dimensional matrix simulates the extracellular matrix (ECM) found between a capillary, or parent blood vessel, and the RPE layer. When an RPE cell secretes VEGF, it diffuses through the ECM towards the capillary. As VEGF levels at the capillary increase, endothelial cells (ECs) secrete protease, which degrades the fibronectin found outside the capillary. EC movement is based on a random number generated by concentration of protease, fibronectin, and VEGF at the surrounding points. This random number determines the probability that the cell will move, die, or proliferate once it enters the ECM. PEDF is secreted from the same location as VEGF but diffuses at a slower rate, interacting with the EC by stopping protease production. The percentage of blood vessels that have grown over the total surface area available is calculated along with the number of times the blood vessel branches. Scenarios with varying levels of VEGF and PEDF were repeated 30 times and averaged.
Results :
The computational model shows increased blood vessel growth with increased VEGF concentrations. However, once VEGF concentrations reach a certain threshold, blood vessel coverage begins to decrease. Max blood vessel growth occurred 3-5 hours after the simulation started. Increasing levels of VEGF caused the blood vessels to have more branches than lower levels of VEGF with the same blood vessel coverage. When VEGF and PEDF levels were in healthy amounts, no blood vessel growth occurred. An endothelial cell angiogenesis assay was used to validate results.
Conclusions :
Computational modeling is a powerful tool with parameters that can be modified to mimic retinal disease pathologies. This computational model gives new insights into exudative AMD, including max growth times and the effects of VEGF and PEDF on angiogenesis in the eye. This model can be adjusted as research continues to better match what is seen in vivo.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.