Retinitis pigmentosa gene discovery may reveal a new route to inherited blindness

November 24, 2016 by Fight For Sight

Researchers at UCL Institute of Ophthalmology and Moorfields Eye Hospital with funding from Fight for Sight, in collaboration with a team from Baylor College of Medicine in the USA, have discovered a new retinitis pigmentosa gene. The team used gene editing to confirm that faults in receptor expression enhancer protein 6 (REEP6) cause 'rod' photoreceptor cell degeneration. Their results point to a biochemical pathway that was previously unknown to be important for the retina.

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, affecting 1 in 4000 people. In RP, light-detecting photoreceptor cells in the retina at the back of the eye degenerate and die over time. It starts with the photoreceptors that are active in low light – the rods – and may later progress to the 'cones' used for seeing colour and detail.

Exactly how RP develops will depend on the specific gene or fault involved. To date there are at least 58 genes linked to autosomal recessively inherited RP, but an estimated 1 in 4 people with RP do not yet have a precise diagnosis. Autosomal recessive conditions are those caused by inheriting two faulty copies of a gene, one from each parent.

In the current study, the research team used whole genome sequencing to identify 6 different faults in REEP6 in people with RP from five unrelated families in the UK and USA. The faults were identified in both copies of the gene in keeping with an autosomal recessive inheritance pattern.

Professor Mike Cheetham at UCL Institute of Ophthalmology was the study's UK lead. He said:

"REEP6 encodes a protein that has not been studied intensively before. We were able to show in human photoreceptors derived from patient stem cells that REEP6 is highly active in rod photoreceptors. We were also able to confirm using CRISPR-Cas9 gene editing that introducing one of the REEP6 variations associated with RP into mice led to symptoms that closely mimic the pattern of photoreceptor degeneration we see in these patients.

"Although we know little about the precise function of REEP6 inside rods our results are interesting and important because the related genes we do know about have not previously been linked to retinal dystrophy. We now have an accurate genetic model of this form of RP in which to investigate further and have shown the usefulness of to study genetic diseases."

Dr Dolores M Conroy is Director of Research at Fight or Sight. She said:

"We are very pleased to see that more families with inherited retinal blindness are able to have a specific genetic diagnosis. This is both the start of better information around which to plan the future and an important first step on the road to developing treatment. The collaborative working between major centres of genetic research as supported by the RP Genome Project co-funded by Fight for Sight and RP Fighting Blindness is progressing as we intended."

Explore further: A new mode of communication between donor and host photoreceptors in retinal dystrophy

More information: Arno et al., Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa, The American Journal of Human Genetics (2016).

Related Stories

A new mode of communication between donor and host photoreceptors in retinal dystrophy

October 24, 2016
UK eye researchers with funding from Fight for Sight have discovered a new means of communication between transplanted donor photoreceptors developed from stem cells and the degenerating photoreceptors of the host retina. ...

Gene therapy gives long-term protection to photoreceptor cells

July 15, 2015
A collaboration between scientists in the UK and the USA has shown that gene therapy can give life-long protection to the light-sensitive photoreceptor cells responsible for colour vision in a mouse model of the most common ...

Rescuing human light-sensors in a common form of Leber congenital amaurosis

April 14, 2016
Scientists at the UCL Institute of Ophthalmology have identified the mechanism behind a common inherited cause of severe sight loss in young children. The results also point to a potential new treatment that may be possible ...

Researchers identify treatment target for blinding diseases

September 28, 2016
New research published in Cell Reports identifies a potential treatment target for blinding diseases such as retinitis pigmentosa and advanced dry age-related macular degeneration. In the study, researchers at Washington ...

Retinitis pigmentosa may be treated by reprogramming sugar metabolism

November 14, 2016
Columbia University Medical Center (CUMC) researchers have demonstrated that vision loss associated with a form of retinitis pigmentosa (RP) can be slowed dramatically by reprogramming the metabolism of photoreceptors, or ...

New form of inherited blindness discovered

May 14, 2015
Scientists from the University of Leeds, in collaboration with researchers from the Institute of Ophthalmology in London and Ghent University in Belgium, have discovered that mutations in the gene DRAM2 cause a new type of ...

Recommended for you

Genome analysis with near-complete privacy possible, say researchers

August 17, 2017
It is now possible to scour complete human genomes for the presence of disease-associated genes without revealing any genetic information not directly associated with the inquiry, say Stanford University researchers.

Science Says: DNA test results may not change health habits

August 17, 2017
If you learned your DNA made you more susceptible to getting a disease, wouldn't you work to stay healthy?

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Evolved masculine and feminine behaviors can be inherited from social environment

August 15, 2017
The different ways men and women behave, passed down from generation to generation, can be inherited from our social environment - not just from genes, experts have suggested.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.