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C. Punzo, C. L. Cepko; Starvation: A New Mechanism for Cone Death in Retinitis Pigmantosa. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5192.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis Pigmentosa is an inherited disease that affects rod and cone photoreceptors. Interestingly, in most cases the disease causing allele encodes for a gene that is exclusively expressed in rods, nonetheless, cones die too. We were interested in understanding the cause for this rod mediated cone death in Retinitis Pigmentosa.
To understand the mechanism of non-autonomous cone death, four mouse models harboring mutations in rod-specific genes were analyzed. Affymetrix mouse arrays were used to study the gene expression changes at the onset of cone death.
We found that autophagy is activated in cones during cone degeneration. Autophagy was due to nutrient deprivation. This nutrient shortfall coincided with changes in the insulin/mTOR pathway, a key pathway in regulating cellular homeostasis. Those changes suggested that glucose availability in cones was especially compromised during cone degeneration. Based on these observations we treated animals with insulin and found improved cone survival.
The data suggest that the non-autonomous cone death in Retinitis Pigmentosa is at least in part due to starvation of cones caused in part by a shortage of glucose. We therefore propose a model where the cone outer segment retinal-pigmented epithelium interactions are perturbed during rod death, which results in a reduced flow of nutrition to cones.
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