The role of inflammation in age-related macular degeneration

Why is this research needed?

Age related macular degeneration (AMD) is the leading cause of sight loss in the developed world. There are two types of AMD: dry AMD (also called geographic atrophy, GA) and wet AMD (neovascularisation). Over 80% of people with the disease have Dry AMD, for which there is currently no treatment.

Dr Chen is investigating the role of inflammation, specifically a molecule SIGIRR, in causing dry age-related macular degeneration (AMD). Through years of research, inflammation has been shown as an important factor that damages the macula in AMD, and it is thought that properly controlled inflammation may be able to slow down or halt AMD progression. Inflammation is part of the body’s natural defence mechanism: protecting it from harmful agents, such as bacteria or viruses, and playing a role in the healing process. 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. Within the body’s 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.

Eyes donated from patients with dry AMD have been found to have less SIGIRR compared with eyes from healthy donors. Previous research suggests that insufficient SIGIRR may be a key reason for uncontrolled inflammation in AMD. Therefore enhancing SIGIRR expression could be a new approach for immune therapy.

What is the aim of the project?

Dr Chen is seeking to understand why loss of SIGIRR leads to uncontrolled inflammation in AMD, and whether the development of this disease can be delayed or halted by enhancing the molecule SIGIRR, through gene therapy.

How will this research help to beat sight loss faster?

Currently, there is no therapy for dry AMD. Dr Chen’s research project aims to provide essential evidence to establish the role 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 knowledge could lead to new ways to predict the progression of AMD and effective approaches to treat dry AMD.

This PhD project is jointly funded by Sight Research UK and Fight for Sight.

Further information

You can find more about the causes and symptoms of AMD here.