Restoring visual function after photoreceptor degeneration: ectopic expression of photosensitive proteins in retinal neurons

Abstract

A leading cause of blindness worldwide is degeneration of the retinal photoreceptor cells. The two large classes of such disorders are retinitis pigmentosa, which affects ∼100,000 individuals in the USA, and macular degeneration, which affects ∼3,000,000. The causes of both disorders are diverse, but the initial lesion in both cases is to the rod and cone photoreceptor cells, leaving a retina in which many neurons appear functionally intact, but the retina – either the entire tissue or specific regions of it – can no longer detect light. A strategy for restoring at least a minimal level of vision is to engineer the expression of a photosensitive molecule in the surviving, nonphotoreceptor, neurons. This has been achieved at the level of proof of principle in the rd strain of mice, which undergoes photoreceptor degeneration similar to retinitis pigmentosa. In separate experiments, Channelrhodopsin-2 or melanopsin were introduced into retinal neurons and restoration of electrophysiological responsiveness and simple visually guided behaviors was demonstrated. There is reason for cautious optimism that vision aided in this way may eventually be of use for humans suffering from photoreceptor degenerations.