Our members and researchers have been updating us on their recent efforts and we are very proud to highlight their work here.
In conversation with… Dominique Sturz
‘In conversation with…’ is Retina International’s new interview series where we speak with key figures in our community of patients, advocates, researchers, clinicians and policy makers. The aim is to highlight the work of our community and share information and experiences. Our first conversation is with Dominique Coordinator of RI-USH SIG, Patient Advocate for Usher Syndrome & Rare Eye Diseases, Dominique Sturz talks with Retina International about her experiences in patient advocacy for Usher Syndrome and her plans for the future. You can read it here https://retina-international.org/in-conversation-with-dominique-sturz/
The eyeless worm sheds light on inherited retinal degenerations
Fighting Blindness Ireland are delighted to announce the commencement of exciting ‘curiosity-driven’ research at University College Dublin as part of the Irish Research Council Enterprise Partnership Scheme. Entitled ‘Cilia-related inherited retinal dystrophy; uncovering fundamental disease mechanism and designing patient-oriented impact’ this study aims to unearth important fundamental cilia biology relevant to ciliopathy diseases.
Cilia are slender, microscopic, hair-like structures that extend from the surface of nearly all mammalian cells, including retinal cells. They act like microscopic train-tracks and allow the transport of vital molecules from one end of the photoreceptor to the other. Dysfunction or defects in cilia are now understood to underlie a number of genetic forms of retina conditions such as cone-rod dystrophy, Usher syndrome and Bardet-Biedel syndrome. Collectively, these are termed ciliopathies.
Through studying the ‘eyeless’ nematode worm (C.elegans), Prof Blacque discovered that a protein called Rab28 operates in the primary cilia. Since then the team have shown that in mice and zebrafish, this Rab28 protein functions in the photoreceptor cell’s outer segment (modified cilium). However, very little is known about what exactly Rab28 is doing in cilia, how its function relates to ciliopathy proteins, and how its disruption can result in sight loss.
This three year project thus aims to increasing understanding of Rab28 and potential role in cone-rod dystrophy. In addition, together with Fighting Blindness, it will develop patient-oriented strategies towards greater public awareness and engagement of ciliopathy-related inherited retinal degenerations.
Retina UK
Research Update
The first quarter of 2019 has seen some very positive results from research funded by Retina UK. This includes:
New developments in the search for treatments for Stargardt disease
Researchers have developed a fast, cost-effective method of scanning the entire length of the ABCA4 gene, including the introns. The new method has enabled them to find several intron mutations in cells from people living with Stargardt’s and they have gone on to develop a kind of molecular patch, described as a “band aid”, to cancel the harmful effects of these mutations. Read more http://bit.ly/2uQVBFs
Promising interim results for trial of potential new treatment for LCA10
Further confidence in QR-110’s potential to produce meaningful benefits to those living with LCA10, a severe childhood-onset inherited retinal disease causing early vision loss has been published in a highly regarded peer review journal. Read more http://bit.ly/2UEBGIj
We will be publishing more detailed information about current research and the researchers themselves in our Look Forward Newsletter, due out in mid-April.
Our Community’s voice
The very first Retina UK audience insight survey opened in mid-March, asking those affected by inherited sight loss to tell us about their experiences and what really matters to them.
The response rate so far has exceeded our expectations, with 700+ surveys completed. The findings will guide the charity on the role the inherited sight loss community would like us to play in supporting and representing them in the future.
BBC Radio 4 In Touch
Tina Houlihan, CEO of #TeamRetinaUK talked about our Community Survey and current research into retinal conditions and treatments on BBC Radio 4 on Tuesday 5 April https://bbc.in/2D1ZThV.
Remembering RIWC2018 as we look to RIWC2020
Auckland, the pacific meeting place was host city for the 2018 Retina International World Congress in early February. Some 422 delegates including patients and their families, clinicians, scientists, rehabilitation professionals, students and anyone with an interest in retinal disorders were stimulated and enthused by the 4-day programme of short scientific presentations, expert panels, treatment approach plenaries, Retina International business and learning meetings and social events. With speaking contributions from acclaimed clinicians and scientists from Australasia, North America and Europe, a comprehensive review of progress in the retina was skilfully-pitched to an audience who greatly appreciated this rare in-person opportunity. From the opening plenary to the closing “where are we now and what does the future promise” session, the tone was optimistic, realistic and collegial. Among the clinical advancement highlights, it was particularly exciting to be able to hear from and congratulate Professor Jean Bennett, co-director, Centre for Advanced Retinal and Ocular Therapeutics, University of Pennsylvania. Professor Thiran Jayasundera’s session “Argus 2 – the surgical procedure and clinical journey”, delivered in a broad spectrum Artificial vision plenary, was an intriguing insight into many aspects of delivering functional vision – the kiwi-trained surgeon following a dream, the patient experience and a look into the future. Totally blind author and accessibility specialist Jonathan Mosen presented a thought-provoking and empowering examination of the impact of advancement in digital technology on people with sight loss.
Pre-clinical research pipe-line established at AMC Amsterdam with NEI
Together with collaborators of the National Eye Instute (Dr Kapils’ lab), the Ophthalmogenetics team of Prof dr Arthur Bergen at the AMC Amsterdam has recently set up a medium throughput, pre-clinical research pipe-line, which combines the possibilities of experimental stem cell therapy, gene therapy and small molecule therapy with IPS stem cell derived retinal organoids and transplantation research (Appendix A and B).
According to Prof Bergen: “the rationale behind this, is that every (genetic retinal) disorder will require it’s own type of optimal (combination) therapy in the future; accordingly, one local flexible research infrastructure to study these disorders is ideal.” The lab is focusing currently on disorders affecting primarily the RPE (AMD, gyrate atrophy, albinism) and ganglion cells (glaucoma).
“With this platform and direct access to the Amsterdam Ophthalmogenetic Archives, build up since the 1960’s, and containing clinical records of 20.000 patients with eye disorders and thousands of certified DNA diagnosis in 9000 families, the possibilities for therapeutic research and clinical trials for retinal disorders are virtually unlimited,” says Prof Camiel Boon, currently clinical P.I. in Amsterdam, and closely collaborating with the Bergen team (aabergen@amc.uva.nl)
Some of this research was presented by promising young investigators: Dr Mays Talib, Dr Celine Koster and Dr Philiph Wagstaff, at the ARVO, USA, May 2019.
Image: ERN-EYE logo
Free Research-based Sequence Analysis of Genes Associated with Rare Inherited Eye Diseases in Centers of Expertise
At the ERN-EYE meeting in Florence on 12 October 2018, research groups from across Europe volunteered to perform sequence analysis to identify the underlying mutations for one or more inherited eye disease(s). This initiative is important as many new centers cannot afford costly Sanger sequencing or next-generation sequencing-based gene-panel sequencing.
This genotyping can only be done in a research setting, and diagnostic validation for clinical use, e.g. via Sanger sequencing of the identified variant(s) in the proband and/or family members, should be done in a certified diagnostic laboratory afterwards.
The research groups involved will benefit from the sequencing as they can study novel causes or mechanisms of disease. It is being spearheaded by Prof. Frans P.M. Cremers, Nijmegen, The Netherlands. You can read more about it in detail here: https://retina-international.org/free-research-based-sequence-analysis-of-genes-associated-with-rare-inherited-eye-diseases-in-centers-of-expertise/
Institute of Molecular and Clinical Ophthalmology Basel (IOB), Switzerland
The Institute of Molecular and Clinical Ophthalmology Basel (IOB) continues its fast ramp-up to accelerate the conversion of basic research into innovative treatments which change the field of ophthalmic therapy based on the genetic, structural and functional understanding of the cell types and their interactions within the human eye. On April 10, 2019, IOB co-director Botond Roska receives the 2019 Louis-Jeantet Prize for Medicine 2019 in Geneva. It is one of the best-endowed awards in Europe to foster scientific excellence, for the discovery of basic principles of visual information processing and the development of therapeutic strategies, such as gene therapy, to restore vision in retinal disorders.
70% of patients have retinal shift after retinal detachment repair. This may lead to distorted vision, binocular diplopia and may be visualized as hyperfluorescent lines by fundus autofluorescence. A prospective randomized study with IOB researchers showed that the use of intraoperative heavy liquid appears to be associated with lower occurrence of retinal shift after retinal detachment repair. The study is published in Ophthalmology Retina https://doi.org/10.1016/j.oret.2019.01.010. You will find a lot of more research and clinical news on www.iob.ch/news; and if you follow @IOB_ch on twitter.
Updates from Enrique J. de la Rosa, Ph. D. 3D Lab, España / Spain
Our group is focused in unraveling the molecular and cellular alterations concomitant to the onset and the progress of Retinitis Pigmentosa. Our aim is not only to better describe the physiopathological mechanism of the disease but also to define new potential therapeutic targets. In the past few years we have carried out proof-of-concept studies with molecules that interfere with processes common to and independent of the causative mutations. Besides studying the neuroprotective role of proinsulin during retinal development and, more recently, in retinal neurodegeneration, we have incorporated small molecules designed to interact with other two potential targets: GSK3 and the neurotrophin receptor p75NTR. Preclinical studies in various mouse models of Retinitis Pigmentosa showed attenuation of photoreceptor cell death, decrease of the proinflammatory response, and, in the tested cases, delay of visual function loss. We are currently studying the role of diverse players of the innate immunity retinal response in the onset and the progress of Retinitis Pigmentosa.
(3D Lab: Desarrollo, Diferenciación y Degeneración (Development, Differentiation & Degeneration). Centro de Investigaciones Biológicas. Consejo Superior de Investigaciones Científicas. Ramiro de Maeztu 9, E-28040 Madrid (España / Spain).
Institute de la Vision, France
At the end of last year, the FOReSIGHT project, coordinated by Professor José-Alain Sahel, received the “IHU – Institut Hospitalo-Universitaire” label, a prestigious distinction awarded by the French government. Supported by the “Voir & Entendre Foundation”, this new entity brings together prestigious institutions (Inserm, Sorbonne University and the Centre Hospitalier des Quinze-Vingts) around the Institut de la Vision in order to meet the current and future challenges of ophthalmology and vision neuroscience.
The Scientific representative of the French Consulate in Los Angeles (USA) and its partners, the Institut de la Vision (France) and the Institut Jules Stein Eye (USA) are organizing a congress on hereditary retinal dystrophies on May 6 and 7, 2019 in Los Angeles, California. This congress will provide a global understanding of retinal degeneration, from epidemiological aspects to the most innovative treatments. The goal of the congress is to facilitate the development of innovation ties between France and America by bringing together scientists, companies and other interested stakeholders. The best scientists and clinicians from France and the United States will be invited to speak. French and American start-ups will be present at this meeting in order to concretize the exchanges between fundamental research and clinical applications. www.institut-vision.org www.fondave.org
Phase 3 gene therapy trials for AMD & CHM originating from Oxford research
In the course of 2018, Professor Robert MacLaren (University of Oxford) was elected as a Fellow of the Academy of Medical Sciences (UK). His recent work includes the successful UK clinical trial of the second-generation electronic retinal implant developed by Prof Eberhart Zrenner and now commercialised through Retina Implant AG (Ophthalmology). In collaboration with Prof Marc de Smet and Preceyes BV in Eindhoven, he also led a first-in-man trial of a robotic device for eye surgery (Nature Biomedical Engineering). The last 12 months have also seen the international launch of a Phase 3 clinical trial, led by Nightstar Therapeutics, of the choroideremia gene therapy, originally developed in the MacLaren laboratory at Oxford University. This Phase 3 clinical trial, which will be recruiting 140 participants in 6 countries, is the largest gene therapy trial for any disease in the world to date. The Phase 3 clinical trial follows on from the successful results of the initial Phase 1 study (Nature Medicine). Most recently, he has started another retinal gene therapy clinical trial, sponsored by Gyroscope Therapeutics, targeting dry age-related macular degeneration (AMD) and using an adeno-associated viral vector co-developed in his laboratory in Oxford.
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