Using mouse models and advanced imaging techniques, Megaw et al reveal the role of RPGR in the retina and the mechanism underpinning vision loss, with possible therapeutic target: May 2024 Image Light sensing cells at never before seen magnification. Work by the Mill group at the Institute of Genetics and Cancer have shed light on a leading cause of childhood blindness.Inherited retinal disorders (IRDs) are a group of genetic eye diseases and the leading cause of visual loss in children and adults of working age in the UK. One of the most common types of IRDs is Retinitis Pigmentosa (RP) which affects 1 in 3000 people. Patients with RP present with night blindness and progressive visual loss as the light sensing cells in the eyes gradually die off.IRDs are mostly untreatable and are caused by mutations in genes crucial for retinal function. A leading disease gene is RPGR and a lack of understanding of the gene’s function has prevented the development of effective treatments.Using humanised mouse models of RPGR-mediated RP and cutting edge imaging techniques, researchers were able to provide fresh insights on the function of the RPGR protein. They found that when RPGR is mutated, the light sensing cells in the eye become unstable and, as a result, are unable to correctly build the part of the cell that detects light. This causes the light sensing cells to become stressed and begin to die, resulting in vision loss. They demonstrated that treating the light sensing cells with a small drug molecule can stabilise them and partially correct the abnormalities.Their findings have provided valuable mechanistic insights into the disease and has shown the potential for RP to be treated with small drug molecules. This could help in the development of new treatments for this devastating disease. Retinitis Pigmentosa causes early onset sight loss. It has no treatment and, if we are to develop any, it is crucial that we fully decipher the disease process. I feel this work brings us closer to understanding RPGR’s role in the light sensing photoreceptor and why patient mutations cause blindness. Dr Roly Megaw Wellcome Clinical Research Fellow(MRC, Human Genetics Unit) By using cryo-electron tomography, scientists were able to look inside the light sensing cells at never before seen magnification. LinksFull article DOI: https://doi.org/10.1038/s41467-024-48639-wMill Research GroupView the article published in the Herald Document Herald Article (11.84 MB / PDF) Tags 2024 Publication date 01 May, 2024
