Dr. Xinhua Shu is a Rosetrees Trust-funded researcher who, with his team at Glasgow Caledonian University, is investigating new treatments for age-related macular degeneration (AMD). AMD is the commonest cause of registered blindness in the developed world, with a global impact estimated to rise to 196 million people by 2020.
Previously, Dr. Shu received funding from Rosetrees to work on retinitis pigmentosa (RP). This is an inherited disease that causes degeneration of the light-sensitive photoreceptor cells in the retina of the eye, leading to progressive loss of vision and ultimately blindness. Dr. Shu investigated possible protective effects of gypenosides, chemical compounds found in Gynostemma pentaphyllum, a plant common to South-East Asia, and how they might shield particular cells in the eye from oxidative stress caused by free radicals, damaging molecules released in the condition (published in Food and Chemical Toxicology). It is hoped that these gypenosides may offer therapeutic potential to patients suffering with RP.
As a result of his RP project, Dr. Shu secured further funding from Rosetrees to work on AMD. It is known that AMD involves the build-up of cholesterol deposits in the retina. Dr. Shu and his team published in Human Molecular Genetics, identifying the part played by a particular cell protein known as TSPO in the removal of cholesterol from the retinal pigment epithelium (RPE), the specialised layer of cells that lies behind the photoreceptor cells. Dr. Shu is now taking his research into new areas with his latest hypothesis, that a defect in cholesterol processing plays an important role in AMD.
In two later publications in the International Journal of Molecular Sciences (2018; 2019), Dr. Shu and his team investigated TSPO ligands, substances that can bind to TSPO and influence its activity. The chronic version of AMD involves changes in the choroid, the layer containing the vessels that supply the retina with blood. Dr. Shu’s group tested treatment of choroidal cells with TSPO ligands. These have shown anti-oxidative stress and anti-inflammatory properties, and the team’s study showed that TSPO ligands may offer promise for the treatment of AMD. Two of these TSPO ligands, Etifoxine and XBD-173, have already gone through clinical trials, demonstrating therapeutic effects in patients with anxiety. This means that, if treatment for AMD can be shown to be successful, these compounds can progress to clinical trials much faster. The group also showed that using genetic manipulation to suppress TSPO activity in RPE cells resulted in changes in various metabolic pathways, including increased oxidative stress. This study should contribute to a deeper understanding of AMD disease mechanisms.
Their findings demonstrate that TSPO is involved in cholesterol removal in the retinal pigment epithelium and that loss of TSPO causes abnormal build-up of cholesterol within cells; TSPO ligands can help improve cholesterol removal from RPE and choroidal cells and can suppress oxidative stress and inflammation. Their ongoing research is testing the protective effects of TSPO ligands in animal models and they are applying for funding to run clinical trials for TSPO ligands to treat AMD patients. They also plan to present their findings at the 35th Asia-Pacific Academy of Ophthalmology Congress, to be held in Xiamen, China, from April, 2020. “Given that people are living to increasingly older ages, macular degeneration of this type is a condition that will affect a growing proportion of the population, having a major detrimental effect on the quality of life of many individuals. Our efforts are focussed on developing potential strategies to treat AMD.” – Xinhua Shu (Reader, Department of Biological and Biomedical Sciences, Glasgow Caledonian University)
Written by: Rebecca Downing and Dr. Xinhua Shu