Blindness from age-related macular degeneration begins with a slow immune-driven attack on the eye’s support cells, and a new lab-grown model aims to watch that attack unfold in a dish. AMD is the leading cause of blindness in the Western world, yet the early immune events that trigger it remain poorly understood. Researchers cannot easily watch human retinal cells and immune cells interact inside a living eye, and animal models do not fully replicate the human disease. This project fills that gap by creating a cell culture system from induced pluripotent stem cells taken from both AMD patients and healthy controls. The team will grow two key cell types—retinal pigment epithelium (RPE) and microglia—and expose them to the stresses that drive AMD, then observe how they respond and communicate. If the model works, it will allow scientists to identify the molecular pathways that turn chronic inflammation into sight loss. That could reveal new drug targets for treating or preventing AMD. Because the system uses human cells, it should also reduce the number of animal experiments needed to test those potential therapies. The model is not yet ready for clinical use, but it provides a fundamental tool for understanding how the immune system damages the retina—knowledge that could eventually speed the development of treatments for AMD and other degenerative diseases driven by inflammation.
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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 NC3R.
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