The scientific day of Retina 2015 focused on some of the outstanding international research into diseases affecting the retina, with a particular emphasis on research that is beginning to move towards clinical trial development.
The conference was officially opened by Minister Aodhán Ó Ríordáin, Department of Justice and Equality, who stressed the importance of listening to patients and making services “a genuine partnership”. Dr Graham Love, CEO of the Health Research Board (HRB), discussed the importance and role of public and patient involvement in health research, and the HRB’s effort to develop and promote their participation. Patient involvement in the research projects it funds is a new focus for the HRB. Specific criteria are being developed for new research applications to incorporate patient involvement at each step of the proposed research, from study design, to participation and to evaluation.
The research presentations began with a remarkable talk from a great friend of Fighting Blindness and inventor of the sub retinal implant, also known as the “bionic eye” Professor Eberhart Zrenner. Prof Zrenner, from the Tubingen Eye Hospital Germany, spoke about his work on transcorneal electric stimulation (TES) for individuals with retinitis pigmentosa (RP). This idea came from basic research with retinal implants in recent years which indicated, among other things, that electrical stimulation of the retina liberates growth factors which may be able to delay retinal degeneration. Outlining the latest human studies, including his own, Prof Zrenner summarised that TES has been found to be safe, with encouraging results. Adverse events to date mainly included dry eye, which he said has always been treatable by artificial tears. A major new study involving 180 patients is now in development.
We also heard from Prof Rocio Herrero-Vanrell, Complutense University of Madrid, Spain. One of her main research areas is how to target drugs to the retina, which is located at the back of the eye. She has special expertise in microencapsulation of drugs for the treatment of these diseases. She discussed her work on biodegradable microspheres (MSs) for the eye, outlining how it may offer an excellent alternative to multiple injections. This method is able to deliver the active substance, for example an age-related macular degeneration (AMD) drug, in a controlled fashion for extended periods of time. It then disappears from the site of injection after delivering the drug. This would negate the need in the future for monthly injections for conditions like AMD and diabetic eye disease.
Meanwhile, Dr Shannon Boye, University Of Florida, summarised efforts to develop gene therapies for photoreceptor-mediated, inherited retinal disease. She reported how her team has demonstrated the ability to restore visually-guided behaviour and preserve retinal structure in several animal models of Leber congenital amaurosis type 1 caused by mutations in the GUCY2D gene (LCA1). Dr Boye told delegates that they are now working with a pharmaceutical company to bring this treatment to the clinic.
Dr Joseph Carroll of the Medical University of Wisconsin explained in his presentation why some of the current widely used methods to image the retina are not sensitive enough to detect early retinal disease and the small degenerative changes that occur. His work is focused on applying advanced imaging techniques to capture the retina with a precision amount of detail. One of the major applications for this type of imaging is now becoming apparent, which is categorising individuals and tailoring the right therapy to the right patient. Dr Carroll believes that natural history studies are fundamentally important for the development of new therapies. These types of studies follow individuals over time and monitor in detail the progression of disease in order to understand them better. He called on all centres to share data on imaging and disease progression and work together to develop more of these studies on every retinal degenerative disease.
Fighting Blindness funded researcher, Dr Breandán Kennedy, University College Dublin (UCD), is investigating new drug pathways that may have a function in slowing down retinal degeneration. He has recently focused efforts on a group of drugs called Histone Deacetylase inhibitors (HDACi). His research has shown that HDACi are effective in restoring visual function and rescuing morphological defects in a zebrafish model of retinal degeneration. These drugs have been controversial in their application for retinal degenerative disease as some of them are known to be toxic. By testing treated and untreated fish by a protein screen, Dr Kennedy has identified the neuroprotective pathway by which these drugs function and will further explore this pathway in order to identify novel drug targets.
The emerging area of research known as optogenetics had a strong focus at this year’s event, with three speakers outlining their different approaches for this exciting area of research. Put simply, optogenetic tools are focused on making cells sensitive to light. This has the potential to revolutionise treatment and restore vision to individuals at end stage retinal degeneration, there is huge interest and research ongoing in the area. Optogenetics is also a mutation independent approach, meaning it has the potential for wider application than current forms of gene therapy that are specific for a particular gene.
Dr Volker Busskamp from the Center for Regenerative Therapies in Dresden (CRTD), Germany explained his approach which is enabling engineered viruses to deliver a photosensitive protein derived from algae, called chanelrhodopsin, into target cells.
Dr Deniz Dalkara, Insituit de la Vision, Paris is extremely focused on the translation aspect of optogenetics – how do we move research from the mouse models of disease to human application. Dr Dalkara has identified the ganglion cells, which are cells in the inner part of the retina, as the universal target for optogenetics as they are usually preserved in individuals with retinitis pigmentosa (RP), when the photoreceptor cells have already undergone cell death. She is now optimising her tools for clinical use in the future.
Dr Jasmina Cehajic-Kapetanovic from the Royal Eye Hospital, Manchester explained her approach which is delivering the human rod opsin protein to target cells in advanced degenerative disease. She believes that her approach may be more readily translatable to human clinical trials as the protein being delivered is of human origin.
All of the speakers were in agreement about the accompaniment of a goggle device with optogenetics in the future. Because cells expressing optogenetic protein are less light sensitive than normal photoreceptors, vision under regular daylight conditions is unlikely to be possible. Special goggles, which mimic the normal retinal activity of capturing vision information, will then amplify the light signal at the appropriate wavelength to enable vision restoration.
Dr Eric Pierce, Director of the Ocular Genomics Institute in Harvard Medical School gave a fascinating talk about his work as a dual clinician and scientist. He explained his Institute’s patient-centred approach, which starts and ends with the affected individual. Each person with an inherited retinal disease wants to find out the genetic cause of their disease and he believes this will help clinicians give a more precise prognosis for patients as well as inform the design of new therapies. Dr Pierce told a story about a six-year-old girl who presented at his clinic with an early onset and severe form of retinal disease.
They began to investigate the cause of disease and screened all of the 238 genes that are currently known to cause various sight loss conditions. However, as is the case with approximately 40% of individuals, they weren’t initially able to find the disease-causing gene. Not to be disheartened the team embarked on a long process of whole genome sequencing with the ultimate discovery of a disease causing mutation in a part of a gene that had been previously overlooked. This was because the mutation was just before the start of a spelling sequence for the gene NMNAT1, but it turned out that this spelling error or mutation was located in a part of the gene vital to its function.
“It’s a long term project taking on a family, it requires a concentrated team effort to find the cause of disease, potentially over many years” explained Dr Pierce. His laboratory have since generated a mouse model of NMNAT1 blindness and are now focused on designing a viral gene therapy for this disease – a truly remarkable testament to the patient focus of his research.
It was a pleasure to also welcome our friend Dr Stephen Rose, Chief Scientific Officer at Foundation Fighting Blindness in the USA. Dr Rose gave an impressive overview of the research funded by the Foundation and also spoke about the strong international collaboration they seek to build. Steve’s many years of experience in working in the area of retina research is such an asset to our organisation, and during our Public Engagement Day he explained much of this exciting work directly to our members.
As a patient organisation, it is crucially important to feature individuals who live with sight loss throughout the day. The day featured an inspiring talk by Áine Mae O’Mahony, who lost her vision in her mid-twenties; Áine Mae now manages a community radio station in Loop Head, Co Clare. The conference also heard from Derry man Jason Smyth, who was diagnosed with Stargardt disease at the age of eight. Jason holds the title of the fastest Paralympian on the planet, having won double gold at in the 100m and 200m at both the Beijing 2008 and London 2012 Paralympic Games. He holds the world record for both evens and is currently training for the 2016 Paralympic Games in Rio de Janeiro.