Researchers led by a team from UCL Institute of Ophthalmology have identified a new cause of dominant Retinitis Pigmentosa, a rare genetic eye disorder that leads to cell loss in the retina. The study, which investigated 22 families with over 300 affected individuals, was published last week in The American Journal of Human Genetics.
“It was a challenge to identify the DNA alterations causing this form of Retinitis Pigmentosa,” explained Dr. Alison Hardcastle, professor at UCL and principal investigator of the study. “Most other changes identified as the cause of retinal diseases affect the sequence (“spelling”) of a gene. In these 22 families, we did not find gene changes. Instead, we identified complex re-arrangements of chromosome 17.”
To investigate these re-arrangements, the researchers used stem cells from people living with this type of RP and, through a painstaking process, turned them into a ‘retina in dish’ to model the condition. They found that the three-dimensional chromosome structure was altered so that a gene called GDPD1 inappropriately made contact with a molecular ‘on’ switch for expression in the retina. This means that the protein production process in retinal cells “reads” the GDPD1 genetic instructions when they should be ignored.
Professor Alison Hardcastle said; “This represents a new mechanism of retinal disease and new understanding of how alterations of the human genome can cause inherited conditions. We hope our discovery and new knowledge will now lead to many more similar discoveries. It was such a pleasure to work with our international collaborators, including researchers in Cape Town and Berlin.”
The team’s breakthrough in understanding the genetic basis for this type of RP means that researchers can start developing potential treatments to slow disease progression and preserve vision.
This research was made possible by Retina UK as the major funder of the UK Inherited Retinal Disease Consortium, with partner funding from Fight for Sight UK.
Full news release: https://retinauk.org.uk/general-news/new-mechanism-of-disease-discovered-for-retinitis-pigmentosa-by-researchers-at-ucl-institute-of-ophthalmology-and-moorfields-eye-hospital/