Photoreceptor death: spatiotemporal patterns arising from one-hit death kinetics and a diffusible cell death factor.
Retinitis pigmentosa (RP) is an inherited disease affecting approximately 1:4000 individuals in North America. It is characterized clinically by the gradual apoptotic death of photoreceptor cells that occurs nonuniformly across the surface of the retina. Recently, it has been demonstrated that the time of death of many individual photoreceptors is random, a fact that must be reconciled with the spatiotemporal patterns of photoreceptor degeneration that are observed in patients with RP. One possible explanation is that a diffusible toxic factor is released by dying photoreceptors and induces adjacent cells to likewise undergo apoptosis. To determine if such a mechanism can result in patchy distributions of photoreceptor death, as frequently observed in RP patients, we studied cell attrition produced by a bistable biochemical switch in an idealized one-dimensional retina. We found that with a reasonable choice of parameter values, our model was able to produce patterns of cell death resembling those observed in RP. In the context of this model, patches on the order of histologically observable size could develop from a single release event, but their rates of formation were independent of the concentration of toxic factor released. Instead, factor concentration affected the overall rate of cell death, the number of degenerating patches, and their distribution across the retina.
Burns
Jonathan
J
Department of Mathematics, University of Toronto, Toronto, Ontario, Canada M5S 3G3.
Clarke
Geoff
G
Lumsden
Charles J
CJ
D017209:Apoptosis / Q000502:physiology*; D004596:Electroretinography; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000473:pathology*