Mr Matt Rutar, Retinal Development and Aging Group, Eccles Institute of Neurscience, JCSMR, ANU
Age-related macular degeneration (AMD) is a retinal disease which affects millions of individuals worldwide, and is the leading cause of blindness in the industrialised world. While the advent of anti-vascular endothelial growth factor (VEGF) therapy has allowed for the effective treatment of neovascular AMD, no effective treatments are available to mitigate ‘dry’ forms of AMD, including geographic atrophy. A direct involvement of the complement system has been recently confirmed through various gene association studies, which have firmly established inflammation as a key factor in the pathogenesis of AMD. However, little is known of the cellular events which govern the activation of complement in the degenerating retina.
Our work investigates the suitability of light-induced retinal degeneration in rats as a model for dry AMD, to explore the spatiotemporal emergence of inflammatory events in the retina. These investigations focus on the expression of genes relating to the complement system, utilising microarray analysis, quantitative PCR, and in situ hybridisation. This is correlated with the recruitment of inflammatory monocytes in the light-damaged retina, and the retinal expression of chemotactic molecules known as chemokines, which mediate their recruitment and activation. Our findings pinpoint monocytes as key factors mediating the synthesis and activation of complement in the degenerating retina, and whose recruitment to the retina may be facilitated in part by chemotactic signals originating from the retina. Therapeutic attenuation of monocyte recruitment may be a useful strategy to control detrimental propagation of complement in the retina, particularly in retinal degenerations such as AMD.