Immunophysical analysis of corneal neovascularization: mechanistic insights and implications for pharmacotherapy

The cornea lacks adaptive immune cells and vasculature under healthy conditions, but is populated by both cell types under pathologic conditions and after transplantation. Here we propose an immunophysical approach to describe postoperative neovascularization in corneal grafts. We develop a simple dynamic model that captures not only the well-established interactions between innate immunity and vascular dynamics but also incorporates the contributions of adaptive immunity to vascular growth. We study how these interactions determine dynamic changes and steady states of the system as well as the clinical outcome, i.e. graft survival. The model allows us to systematically explore the impact of pharmacological inhibitors of vascular growth on the function and survival of transplanted corneas and search for the optimal time to initiatetherapy. Predictions from our models will help ongoing efforts to design therapeutic approaches to modulate alloimmunity and suppress allograft rejection.