Developing an in vitro model to investigate the role of the immune system in age-related macular degeneration

Age-related macular degeneration (AMD) is a complex disease and the leading cause of blindness in the western world. Over time, changes in the retinal pigment epithelium (RPE) leads to the damage of light-sensing cells in the retina and subsequent central vision loss. The immune system plays an important role in the development of AMD. Ageing and stress cause RPE cell damage and the build-up of debris in and around the RPE, resulting in chronic inflammation and an immune response in the macular region. Investigating disease related events that lead to inflammation in the eye will help us to understand the early events leading to AMD pathology and could allow us to develop new therapies to treat or prevent sight loss.

Here, we will develop a new cell culture model to examine the behaviour and interactions of two key cell types involved in AMD, the RPE and immune cells found in the eye, called microglia. To achieve this, we have created induced pluripotent stem cells from patients with AMD and healthy controls. Using these stem cells, we will produce RPE and microglia and study their responses to stresses seen in AMD. Culturing these cells together will also allow us to study the interactions between retinal and immune cells and identify pathways that could be targeted therapeutically.

The immune response to inflammation in the eye plays a pivotal role in the development and progression of AMD. This research project will create a new cell culture-based AMD model system, which will provide a wealth of information on inflammation/immune mechanisms in patient cells. The project will help us to better understand early events leading to AMD pathogenesis and potentially identify undiscovered targets that could be manipulated therapeutically. Reducing chronic inflammation and controlling the immune response could help to treat patients with AMD. This research project will also create a novel cell-based model that could be used to develop and test drugs targeting inflammation/immune responses in degenerative diseases. Ultimately this cell system will reduce the number of animal experiments required to identify pathogenic mechanisms and potential treatments, advancing the pathway to clinic for AMD and other immune-based degenerative diseases.

Research supervision from experts in IPSC disease modelling, degenerative disease and bioinformatics will ensure that the student is trained to carry out these experiments and understands the significance of developing new human model systems in line with the priorities of the NC3Rs.