Factors that accelerate photoreceptor death: The role of purines
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In Australia, 50% of all cases of blindness occur as a result of photoreceptor death, which is the primary cause of vision loss in dry Age Related Macular Degeneration (AMD) and hereditary retinal diseases such as retinitis pigmentosa (RP). Currently, there are no therapies for slowing the progression of vision loss in either dry AMD or RP. Understanding what drives photoreceptor death in these retinal degenerations is crucial for development of therapies for slowing disease progression.
While, the purine ATP is vital for metabolism within the cell, extracellular ATP is known to act as a neurotransmitter in some parts of the CNS including the retina. Recently, we have found that changes in the purinergic signalling pathway are associated with the progression of retinal degeneration. ATP acts on two types of purinergic receptors, P2X and P2Y receptors. P2X receptors in particular, are highly calcium permeable, and have been implicated in neuronal death in the CNS. We are particularly interested in examining whether overstimulation of P2X receptors on retinal photoreceptors contributes to their death. We want to examine how extracellular ATP kills photoreceptors, and examine whether antagonists to P2 receptors prevents photoreceptor death in pre-clinical models of retinal degeneration. This project involves measuring visual function in pre-clinical models of retinal degeneration, detailed structural analysis and also some molecular biology.
Figure 1: High concentrations of ATP cause photoreceptor death.
The highly ordered structure of the normal retina (A). The retina after the injection of ATP which results in photoreceptor loss in the ONL. The retinas were labelled for cone photoreceptors (red), photoreceptor/bipolar cell synapses (green) and cell nuclei (blue). ONL - outer nuclear layer, OPL - outer plexiform layer, INL - inner nuclear layer, IPL - inner plexiform layer, GCL - ganglion cell layer.
Dr Kirstan Vessey, Senior Research Officer
National Health & Medical Research Council of Australia
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