Characterisation of a novel innate-like T cell in the eye as a target tissue in uveitis, spondyloarthropathy (SpA) and related diseases

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Uveitis is a condition affecting a part of the eye called the uvea. It causes painful inflammation, sight loss and blindness in about 22% of patients worldwide. Uveitis mainly occurs in patients who are young or of working age so sight loss and frequent visits to hospital also make it difficult to maintain employment and cause other problems including depression. Uveitis also occurs in 40% of patients suffering from a condition called spondyloarthropathy. This is a disease of the immune system affecting the joints, the entheses (the structures connecting tendons to bone), eyes, bowel and skin and causes a great deal of disability. Currently we do not understand why and how uveitis occurs. At present, there are very few treatments for uveitis. They do not treat all patients and can have serious side effects which can cause blindness in their own right.Research shows us that one type of immune cell, the T cell existing within the organ itself, could be responsible for much of the disease and disability caused by spondyloarthropathy but we do not know that this for the eye . If we knew the type of immune cell present in the eye which causes inflammation it would help us design much better treatments for uveitis as well as spondyloarthropathy. The similarities and differences between the immune cells in different tissues in spondyloarthropathy will help us design the most effective treatments for patients suffering from spondyloarthropathy as well as uveitis. Studying these immune cells has already resulted in very successful treatment for organs which are affected by spondyloarthropathy such as the skin. The goal of our research is to use new methods to discover the types of immune cells, and genes which are responsible for uveitis and to develop successful treatments based on our results. We are expecially interested in one type of T cell which has recently been found by members of the research team to be present in spondyloarthropathy.The Kennedy Institute of Rheumatology has special expertise in research into the cause of diseases which cause inflammation in the body including spondyloarthropathy. Our research group has expertise in a cutting-edge technique called 'single cell RNA sequencing' , This will allow us to use fairly small numbers of cells from the eye to understand which genes and which cells become active in inflammation. This information can be viewed rather like a map and will tell us where the inflammation is located , which cells are causing it and which genes are active when the eye becomes inflamed. It is likely that similar cells will cause inflammation elsewhere in the body in spondyloarthropathy. We can analyse the functions of these genes and cells in order to understand how uveitis and spondyloarthropathy is caused and how it might be successfully controlled. We expect this research will lead to new treatments.We have agreement from a number of specialist surgical centres to provide a small sample from the eye when they are performing a common surgical procedure called a trabeculectomy. This sample is routinely removed as a part of this type of surgery and while it is normally discarded, we now have ethical approval to use it for single cell RNA sequencing in the human eye. This research will take up 40% of Dr Sharma's time and will last for 33 months in total. Dr Sharma has experience in research in eyes and in studying genes involved in uveitis and spondyloarthropathy. Our research team consists of a wide variety of experts in their respective fields to make sure that we complete this research on time and get results of the highest quality and ultimately, to help patients with uveitis and spondyloarthropathy.