Novel therapies for slowing vision loss caused by retinal degeneration

Death of the light sensitive cells of the retina, the photoreceptors, drives visual impairment in a range of diseases collectively termed retinal degenerations. These disorders include inherited retinal degenerations such as retinitis pigmentosa and complex diseases such as age related macular degeneration (AMD). One mechanism that is common to these disorders is failed production and recycling of proteins important for the function of the photoreceptors. Our data indicate accumulation of intracellular waste is likely to be a critical driver of the photoreceptor dysfunction that occurs in retinal degeneration contributing to cell death, resulting in the devastating consequence of vision loss. Using a range of animal models of retinal degeneration, we see that accumulation of cellular waste and slowing of intracellular recycling in the photoreceptors is a common marker of disease progression, correlating with visual functional loss prior to the death of these cells. Our hypothesis is that intracellular waste clearance can be enhanced to slow photoreceptor death in retinal degenerations. The aims of this project are 1) to determine changes in intracellular waste accumulation relative to the rate of photoreceptor death in a range of rodent models of retinal degeneration, 2) to define the molecular pathways contributing to waste accumulation in retinal degeneration and test small molecule drugs that enhance their function in cultured retina and 3) to determine whether therapeutic agents that enhance waste clearance reduce vision loss in models of retinal degeneration. There are currently no treatments for slowing progression of retinal degeneration due to photoreceptor death. The outcomes of this project will define a novel and common mechanism that contributes to the process of retinal degeneration. Finding treatments that enhance recycling of intracellular waste products may slow the progression of vision loss in retinal degeneration regardless of disease aetiology.

Funder: National Health and Medical Research Council
Award Value: $759,311