Grant: Team Grant: Vision, Hearing and Communication Disorders

In recent years a wealth of new information has become available on the causes of retinal diseases such as age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa. This has highlighted two, connected problems: firstly, it is now clear that very many different genetic mutations and pathological mechanisms can underlie any given disease. Secondly, and because of this, some therapeutic approaches might be impractical since they will target only small numbers of patients or might have limited impact on resultant blindness because only one of a number of pathological mechanisms in that disease has been corrected. By instead targeting pathological mechanisms, therapeutic interventions can be made more generally applicable to a wider a variety of disease. For example, work on inhibiting inflammation is relevant to blindness due to age-related macular degeneration and also diabetic retinopathy. In addition, such a molecular approach is ideal for studying potential synergies - more effective outcomes might be achieved by targeting multiple points of a pathogenic pathway e.g. greater impact might be achieved through concurrently targeting protein misfolding, inflammation and cell death in retinitis pigmentosa. Our team of four scientists, all located at one site, have a committed track record in studies of retinal disease. We propose a series of molecular studies in model systems. From this we will select candidate molecules, targeted at correcting retinal cell apoptosis, protein misfolding or inflammation, to take forward into pre-clinical trials in model systems (zebrafish, xenopus, or rodent). Finally, the most promising molecules will be combined to study synergies to improve outcomes.