Download Retinitis pigmentosa gene discovery may reveal a new

Retinitis pigmentosa gene discovery may reveal a new
route to inherited blindness
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 gene editing 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.”
Ends
NOTES TO EDITORS
Publication
Arno et al., Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa, The
American Journal of Human Genetics (2016).
http://dx.doi.org/10.1016/j.ajhg.2016.10.008
Fast facts
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CRISPR-Cas9 is an engineered version of part of the immune system used by bacteria
to defend against invading viruses. The engineered system is used to target precise
locations in DNA, to edit out or, in this case, insert a new genetic sequence.
The RP Genome Project (also known is the UK Inherited Retinal Dystrophy Consortium)
is co-funded by Fight for Sight and RP Fighting Blindness
http://www.fightforsight.org.uk/our-research/research/2014-1509-black/
This project was also supported by The Wellcome Trust, The National Institute for
Health Research (UK), Biomedical Research Centre at Moorfields Eye Hospital, UCL
Institute of Ophthalmology, Fight for Sight UK (grant 1511/12), Moorfields Eye Hospital
Special Trustees, and Foundation Fighting Blindness, USA.
Fight for Sight is the leading UK charity dedicated to funding pioneering research to prevent
sight loss and treat eye disease. Fight for Sight is funding research at leading universities and
hospitals throughout the UK.
Major achievements to date include: saving the sight of thousands of premature babies
through understanding and controlling levels of oxygen delivery; restoring sight by establishing
the UK Corneal Transplant Service enabling over 52,000 corneal transplants to take place;
providing the funding for the research leading to the world’s first clinical trial for choroideremia;
bringing hope to children with inherited eye disorders by co-funding the team responsible for
the world’s first gene therapy clinical trial; and identifying new genes responsible for glaucoma,
retinitis pigmentosa, keratoconus and other corneal disorders, and Nance-Horan syndrome.
Fight for Sight’s current research programme is focusing on preventing and treating agerelated macular degeneration, diabetic retinopathy, glaucoma, cataract and corneal conditions.
We are also funding research into the causes of childhood blindness and a large number of
rare eye disorders.
Fight for Sight contact:
Heather Fanning, Media Officer. [email protected]; 020 7264 3900.