Modelling Three Dimensional Morphology of Retinal Pigment Epithelium

Age-related macular degeneration (AMD) is the primary cause of vision loss in Americans over 65. The retinal pigment epithelium (RPE) is essential for photoreceptor cell health, and its dysfunction is an early AMD indicator. Although RPE shape changes are observed in AMD conditions, detailed morphological understanding is limited. State-of- the-art morphometric analysis focuses on the apical surface in 2D, missing true physiological dynamics. 3D experimental observations of RPE and Corneal Endothelial Cells (CECs) which exhibit similar patterns to RPE, revealed basal infolding and interdigitation, respectively. We developed a computational model using the Cellular Potts Model (CPM) to represent RPE cells in 3D, investigating the biophysical mechanisms of these features. Our findings reveal that cell-cell and cell-matrix adhesion interactions, along with geometric constraints, drive these morphological changes. Variations in adhesion properties significantly affect cellular morphology and organization, and their interplay with geometric constraints results in the observed interdigitation and infolding patterns.