Stimulation of the insulin/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa

Top Cited Papers
Publisher Website
Google Scholar
Abstract
The retinal degeneration disease retinitis pigmentosa is characterized by an initial loss of rod photoreceptors followed by a progressive loss of cones. Providing a mechanism behind the long delay of cone death in retinitis pigmentosa, Punzo et al. identify and characterize the involvement of an insulin/mTOR pathway, indicating that cell starvation of cones can partially account for the nonautonomous photoreceptor death in retinitis pigmentosa. Retinitis pigmentosa is an incurable retinal disease that leads to blindness. One puzzling aspect concerns the progression of the disease. Although most mutations that cause retinitis pigmentosa are in rod photoreceptor–specific genes, cone photoreceptors also die as a result of such mutations. To understand the mechanism of non-autonomous cone death, we analyzed four mouse models harboring mutations in rod-specific genes. We found changes in the insulin/mammalian target of rapamycin pathway that coincided with the activation of autophagy during the period of cone death. We increased or decreased the insulin level and measured the survival of cones in one of the models. Mice that were treated systemically with insulin had prolonged cone survival, whereas depletion of endogenous insulin had the opposite effect. These data suggest that the non-autonomous cone death in retinitis pigmentosa could, at least in part, be a result of the starvation of cones.