Abstract
Purpose::
Age-related macular degeneration (AMD) is the most common cause of legal blindness in the elderly in the western world. Multiple environmental risk factors contribute to disease progression, and exudative AMD is characterized by choroidal neovascularization (CNV). The purpose of this study is to develop a computer simulation of the processes that lead to CNV and CNV growth in AMD.
Methods::
We developed a computer simulation model of CNV in AMD from the Glazier-Graner Cellular Model, which is well validated for modeling the structural development and physiology of embryonic tissues at the cell level, as implemented in the open-source software package CompuCell3D (downloadable from https://simtk.org/home/compucell3d/).
Results::
The model has been fully tested and recapitulates structure of the normal retina, including the capillary layer and its supporting cells and extracellular matrix, Bruch’s membrane, the RPE cells and the photoreceptor layer. It also properly models the oxygen balance in the tissue, the secretion and degradation of extracellular deposits and their effect on oxygen balance, production of VEGF-related factors by RPE cells in response to hypoxia, and proliferation and secretion of ECM degrading factors by the capillary in response to VEGF-related factors. Our model recapitulates the effect of various insults on drusen formation and CNV, including local loss of vasculature, of RPE-cell death, externally-induced hypoxia and reduced permeability of Bruch’s membrane. The model conforms to the dynamics of the capillary layer and compares favorably with experimental data in the mouse model. In particular, the growth of CNV has been quantitatively compared with the results from experimental CNV in a mouse model.
Conclusions::
A testable computational model has been developed successfully. The results of the simulations recapitulate the biologic development of CNV in AMD. The model may be used to quantitatively simulate the biologic processes that lead to CNV, as well as to test the utility of various combinations of pharmacologic intervention for the treatment of CNV in AMD.
Keywords: computational modeling • age-related macular degeneration • retinal neovascularization