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New Macular Degeneration genes mapped

X-linked retinoschisis (XLRS) is a genetic disease caused by mutations in the retinal protein retinoschisin. The protein plays a crucial role in the cellular organisation of the retina, assbling itself to form paired octameric (consisting of eight retinoschisin) rings.{{quote-A:R-W:450-Q:The research team held out the possibility that future work could lead to genetic interventions and treatments, which could limit or prevent the damage caused by XLRS}}XLRS can lead to a type of macular degeneration in which the inner layers of the retina split, causing severe vision loss and gradual blindness. The disease is said to cause blindness in one in 5,000 males. Currently, there is no effective treatment for XLRS, with research focused on understanding how the disease occurs in the retina.The team of researchers undertook a structural analysis of the disease, using a cryo-electron microscope to examine the protein’s paired rings as well as the effects on the rings of two XLRS-causing mutations. The effects of these mutations, despite being reported to cause the disease, were unknown and could offer explanations on how the normal protein functions in the retina.{{image2-a:r-w:400}}Professor Claire Baldock, professor of biochistry at the University of Manchester and lead author of the research team’s resulting paper, said the cryo-electron microscopy allowed the researchers to identify the location of the mutations on the rings.“We found that one disease-causing mutation sits in the interface between the octamer rings, causing retinoschisin to be less stable. The other mutation is on the propeller tip which we think is a novel interaction site for other binding proteins in the retina,” she said.As well as identifying the mutations and precisely mapping their locations, the research team held out the possibility that future work could lead to genetic interventions and treatments, which could limit or prevent the damage caused by XLRS.