System could combat child blindness

Leber congenital amaurosis, a condition that affects two to three out of every 100,000 newborns, occurs when mutated genes fail to produce RPE65 proteins in the retinal pigment epithelium (RPE), a cell layer critical for protecting photoreceptors.{{quote-A:R-W:450-I:2-Q:“We believe this technology can deliver almost any type of gene to tackle inherited visual disorders,”-WHO:Zheng-Rong Lu, Research Lead Professor}}The protein is an essential constituent of the visual cycle that converts light to electrical signals to the brain and its absence leads to profound vision loss from birth.However, the recently designed lipid-based nanoparticles, called ECOs, were able to deliver healthy RPE65 genes to RPE cells in mice with a form of the disease called LCA2, in the process restoring their vision. The breakthrough has raised hopes that the same technique will now be able to be applied to a range of congenital diseases in humans with similar affects.“We believe this technology can deliver almost any type of gene to tackle inherited visual disorders,” research lead Professor Zheng-Rong Lu said.According to vision scientist and fellow researcher Professor Krzysztof Palczewski one of the major benefits of the method is that it is localised to the photoreceptor cells and therefore spares the liver and kidney from exposure.This is achieved by coating the exterior of the nanoparticle with nucleic acids that function as targeting agents, drawing the delivery syst to the retina and facilitating uptake by RPE cells. ECO also uses a protein found in the eye as an anchor, meaning the gene is only delivered once bound.The team used fluorescent markers to track the process. Following injection into the retina of mice, the researchers could see fluorescent green concentrating in RPE cells. Subsequent testing showed a significant increase in light-induced electrical activity from the eyes to the brain, which indicated the rods and cones were operating as they should in the visual cycle.The therapeutic effect lasted 120 days in treated mice, while no improvents were observed in untreated mice.Palczewski said the work was important beyond one disease, as the loss of photoreceptor cells affected virtually everybody due to ageing. Disease or an injury to the retina also can cause the loss of protective proteins in the cells, resulting in additional cell death and the technology could potentially be applied to protect these aged or damaged cells.Lu and his team are now studying the potential of the ECO syst on other visual disorders such a Stargardt disease, which is a form of genetic juvenile macular degeneration. They are also investigating whether the nanoparticles can be used with the CRISPR/Cas9 gene-editing technique to treat genetic lesions related to retinal degenerative diseases.