Retinal Cell Damage and Repair
My research has been focused on degenerative diseases of the retina, from the molecular and cellular level, to the clinical. My published work has made an impact in two particular areas: (1) The role of oxygen levels in the stability and degeneration of photoreceptors; and (2) the retina's ability to self-protect against stress, using the regulated expression of protective factors. In the former area I was the first to demonstrate the oxygen dependence of several forms of photoreceptor degeneration; in the latter I have shown the sites of trophic factor binding to organelles of the photoreceptor. These lines of research have led to the formulation and testable hypotheses concerning the mechanisms that either damage or protect photoreceptors. Using the light-induced model of retinal degeneration, I was able to test the effects of protective factors and investigate their action mechanism on the stressed retina. To characterise this model further, I started to investigate the role of mitochondrial damage, metabolic changes and oxidative damage in light-induced photoreceptor injury.
In the past 5 years I have been working on cell biology-based, non-invasive therapeutic approaches to manage retinal degenerations. I have been assessing the effects of light management in collaboration with Professor Jonathan Stone (USYD), photobiomodulation (using near-infrared light irradiation) in collaboration with Professor Janis Eells (University of Milwaukee, US) and dietary saffron in collaboration with Professor Silvia Bisti (University of L'Aquila, Italy) on the progress of retinal photoreceptor damage or death. I tested these approaches on models of retinal degeneration, with both environmental and genetic background. I was able to demonstrate that light management is a relatively simple and cost-effective way to slow retinal degeneration, at least in some forms of retinal degenerations (in the P23H-3 model). I also showed that photobiomodulation can slow degeneration in the developing P23H-3 retina, as well as protect from light-induced degeneration. Experiments with saffron supplementation also showed that it is potentially a valuable tool in slowing or preventing some forms of degenerations. In collaborations with Dr Ulrike Mathesius (RSB, ANU) we are exploring effects of photobiomodulation on protein level changes.
In the past 3 years I have started to look at the role of complement in the initiation and maintenance of retinal degeneration. In collaboration with Professor Jan Provis (ANUMS), we are investigating the events that activate the complement system and could be responsible for the loss pf photoreceptors leading to blindness in conditions such as age-related macular degeneration (AMD). Recently, I formed collaboration with Professors Girish Kotwal (US), Goδmundur J. Arason (Iceland) and Gudni À. Alfredsson (Iceland) to investigate the possible beneficial effecto of a novel complement inhibitor in the retina.