Modelling experimental uveitis: barrier effects in autoimmune disease

Abstract

Objective and design A mathematical analysis of leukocytes accumulating in experimental autoimmune uveitis (EAU), using ordinary differential equations (ODEs) and incorporating a barrier to cell traffic. Materials and subjects Data from an analysis of the kinetics of cell accumulation within the eye during EAU. Methods We applied a well-established mathematical approach that uses ODEs to describe the behaviour of cells on both sides of the blood-retinal barrier and compared data from the mathematical model with experimental data from animals with EAU. Results The presence of the barrier is critical to the ability of the model to qualitatively reproduce the experimental data. However, barrier breakdown is not sufficient to produce a surge of cells into the eye, which depends also on asymmetry in the rates at which cells can penetrate the barrier. Antigen-presenting cell (APC) generation also plays a critical role and we can derive from the model the ratio for APC production under inflammatory conditions relative to production in the resting state, which has a value that agrees closely with that found by experiment. Conclusions Asymmetric trafficking and the dynamics of APC production play an important role in the dynamics of cell accumulation in EAU.