Speaker
Description
Retinitis Pigmentosa (RP) is a group of genetically heterogeneous retinal diseases characterized by the progressive loss of rod and cone photoreceptors, leading to irreversible blindness. While genetic mutations in RP primarily affect rods, secondary cone degeneration inevitably follows.
This phenomenon is linked to the loss of rod-derived cone viability factor (RdCVF), a rod-secreted protein that stimulates aerobic glycolysis in cones to support the metabolic demands of outer segment (OS) renewal. To understand these complex mechanisms, we use mathematical models to investigate the dynamics governing photoreceptor dynamics. We first developed a system of nonlinear ordinary differential equations to model RP progression. Through stability, global sensitivity, and bifurcation analyses, we identified key parameters driving the transition from health to blindness. Our results interpret model equilibria as distinct degenerative states and reveal that stable limit cycles emerge at critical junctions, suggesting specific windows for therapeutic intervention. We find that the balance between OS shedding and renewal is vital for cone preservation. Next, we developed a spatially-dependent model to include photoreceptor density distributions and nutrient diffusion. The model was validated against experimental data, accurately predicting OS length and regrowth. These findings establish a foundation for exploring various retinal pathologies and spatial treatment strategies.
