Our research 2018 funded research Dr Mei Chen - Queen’s University Belfast National Eye Research Centre has teamed up with Fight for Sight to fund a PhD investigating aspects of age-related macular degeneration (AMD), the main cause of sight loss in developed countries. Brief background and need for the researchAge related macular degeneration (AMD) is the leading cause of blindness in the aged population in developedcountries. There are two types of AMD: dry AMD (also called geographic atrophy, GA) and wet AMD (neovascularisation). Dry AMD accounts for over 80% of AMD incidence, and currently there is no treatment forit. Through years of research, we now know that inflammation is an important factor that damages the macula in AMD, and properly controlled inflammation may be able to slow down or halt AMD progression. Inflammation is the response of the defence system of our body to take care of us and keep us in order. Inflammation is a double-edged sword: too much inflammation can cause damage to surrounding tissues and too little is ineffective in protection. To overcome this problem, inflammation needs to be carefully controlled. Indeed, within the defence system, some molecules are produced to escalate the inflammatory process, whereas others are generated to cool down or turn off the process. One molecule that can turn off the inflammatory process is called SIGIRR. Researchers have found that without SIGIRR, animals with cancer, asthma or arthritis have uncontrolled inflammation and more severe symptoms. By contract, higher levels of SIGIRR reduces inflammation. We have found that eyes donated from dry AMD patients have less SIGIRR compared with eyes from healthy donors. Our results suggest that insufficient SIGIRR may be a key reason for uncontrolled inflammation in AMD. Enhancing SIGIRR expression could be a novel approach for immune therapy. Aim of the studyWe wish to understand why loss of SIGIRR leads to uncontrolled inflammation in AMD, and whether the development of AMD can be delayed or halted by enhancing the SIGIRR through gene therapy. Method of investigationIn this study, we will firstly investigate how SIGIRR expression changes in normal and AMD eyes using variousadvanced molecular biology and immunology techniques. We will then investigate whether and how age-mediated retinal inflammation is regulated by SIGIRR. Finally, we will use gene therapy to test whether AMD related inflammation and retinal damage can be prevented or reduced by over-expressing SIGIRR in the retina. How achieving your research objectives will benefit patients.Currently, there is no therapy for dry AMD. The proposed study will provide essential evidence to establish therole of SIGIRR in macular inflammation and inflammation-mediated macular damage in AMD. More importantly,the project will demonstrate whether targeting SIGIRR by gene therapy is beneficial in AMD. This might lead tothe discovery of novel biomarkers to predict the progression of the disease, and effective approaches to treat dry AMD.