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Proteasomal stress may represent a key step in the pathobiology of retinitis pigmentosa

New research from Duke University, North Carolina has shown that a cause of photoreceptor degeneration among a number of retinal disease models appears to arise from a failure of cell proteasomes to process abnormally large amounts of mis-folded protein. Researchers at Duke’s Albert Eye Research Institute examined degenerating rods of the transducin gamma-subunit (G-gamma-1) knockout mice, a model in which the rod photoreceptors produce large amounts of transducin beta-subunit (G-beta-1), incapable of folding without the transducin -gamma-subunit. In this model proteaosomal overload quickly reaches a level beyond the capacity of the protein complex to efficiently process the waste eventually leading to cellular shutdown. The researchers additionally suggest that a similar proteasomal overload takes place in photoreceptors of other mutant mice where retinal degeneration arises from protein mis-targeting or mis-folding, but not in models arising from abnormal phototransduction.