Shedding light on unexplained inherited retinal diseases in Ireland and the Netherlands

Prof Frans Cremers, Radboud University, The Netherlands and Prof Jane Farrar, Trinity College Dublin

This gene hunting project falls under the discovery arm of the Target 5000 Programme. Commencing in 2018, this 4-year project is funded by Fighting Blindness. Led by Prof Cremers in the Netherlands with Dr Susanne Roosing, this study brings together expert laboratories, combining complimentary knowledge and skills to shed light on the underlying genetic causes of inherited retinal degenerations.

We spoke with with Prof Frans Cremers and Dr Susanne Roosing at Radboud University, Nijmegen in the Netherlands to learn a little more.

Can you tell us a little more about your research project?

To date current testing methods have revealed the underlying disease causing genetic mutation in approximately 60-65% of inherited retinal degenerations. This means that for the remaining 35%, the genetic cause of disease has yet to be discovered.

Scientists now believe that these hidden variants may be found by searching outside the protein-coding parts of a gene (known as introns).

The teams in both Dublin and the Netherlands will dig deep into these non-coding regions of the genome with the goal of identifying and functionally validating new genetic causes of inherited retinal degenerations, with a focus on Stargardt disease and Usher syndrome.

Overall, this exciting study will lead to new insights to decipher the ‘dark matter’ in IRDs.

To learn more about the Target 5000 Programme please click here.

What attracted you to retinal research?

Prof Cremers: During my PhD, I cloned the gene underlying choroideremia, an X-linked retinal dystrophy which clinically resembles retinitis pigmentosa (RP). This was the first retinal disease-associated gene identified without prior knowledge on the biochemical defect, and thus provided a great starting point to identify other retinal disease genes.

My visit to the Retina International meeting, in which I met persons with IRDs and severe vision impairment, made such a big impression on me that I knew what my goal would be in the rest of my career: finding the genetic defects for as many IRD-associated genes as possible. My team since then discovered more than 30 genes implicated in IRDs.

Dr Roosing: I joined the research team of Frans in 2007 as a lab technician. Previously I was unfamiliar with retinal diseases, but I learned fast about the impact on life when having to live with these degenerative conditions. I got the opportunity to start my PhD project on the topic of cone dystrophies when sequencing all human genes became possible. The excitement to find a missing piece of the puzzle has never gone away.

Within the next five years, where do you expect great advances to be made in vision research?

Prof Cremers: I think the new “CRISPR-Cas” gene-editing technology, that allows correction of genetic defects in a very precise manner, may have a big impact on all IRDs.

Dr Roosing: The awareness that variants that lie in regions of genes that do not encode parts of the protein can also cause disease is increasing rapidly. This expansion of knowledge is highly relevant to establish a genetic diagnosis for all patients for (possible) inclusion for genetic therapies.