Our Retina 2013 Scientific Conference was held in Croke Park on November 8 and 9. The conference was divided over two days: Friday, November 8 was the Scientific Programme, open to all scientists, researchers, and clinicians, and Saturday, November 9 was the Public Engagement Day, open to all patients and members of the public interested in medical research.
Scientific Programme – Friday, November 8, 2013
Leading international researchers discussed hot-button issues such as stem cell research and genetic therapy, as well as the latest treatments for AMD—a disease that affects 1 in 10 adults over the age of 50 in Ireland. Representatives from patient organisations also spoke about the importance of patient involvement in issues related to the progress of medical research to enable the development of treatments for unmet medical needs and to ensure they are part of any discussion around health policies.
The Scientific Programme included top international scientists in the field of vision research, below is a brief summary of their presentations.
John Flannery – Optogenetics for RP
John Flannery is a Professor of Vision Sciences in the University of California, Berkeley and is also a member of the Medical and Scientific Board of Fighting Blindness. A specific area of John’s research focuses on optogenetics for vision restoration, which essentially involves creating “artificial” photoreceptors. This is achieved by engineering light sensitive properties to non-light sensitive retinal neurons using a gene therapy approach. The advantage with this method, as John explained, is that even though the rod and cone photoreceptor cells in the outer nuclear degenerate over time in conditions such as retinitis pigmentosa (RP), the remaining cells of the inner retina such as the ganglion cells and bipolar cells stay surprisingly intact, which makes them a potential target for treatment with this technique.
During the conference, John reported on an improved, second generation photo-switch system that is activated by white light, which relaxes spontaneously in the dark and is ten times more sensitive than the previous systems. He showed that delivery of these photo-switches can restore innate light dependent behaviour in mice. Mice naturally prefer the dark, and mice with no light perception that were treated with these photo-switches demonstrated increased light avoidance behaviour compared to non-treated mice. However mice are not very visual creatures, and in order to further test these novel tools, they are developing sophisticated visual tests to test optogenetic treatment in dogs that are affected by similar retinal degenerations to humans. He is happy to report that thus far the treatment is well tolerated by the dogs and they hope to refine the technology further to help progress this revolutionary science to a clinical setting.
Christian Grimm – Hypoxia in AMD
Christian Grimm from the University of Zurich in Switzerland delivered a wonderful presentation with a snappy title: “Short of Breath: the Hypoxic Response of the Retina”. He explained that the photoreceptor cells in the eye are some of the most oxygen hungry cells in the entire body. This is especially the case at night-time when there is very low light or complete darkness which means the photoreceptor cells have to work harder and therefore consume more oxygen. This can lead to borderline hypoxia which simply means that there are reduced levels of oxygen in the cell.
Christian’s team have shown that hypoxia is a very important process that is essential for early eye development as it allows the formation of blood vessels in the retina. However, he also demonstrated that one of the crucial hypoxia regulators, HIF1α, may be safely inactivated in adult photoreceptors once the cells have already passed this crucial early development. He believes that “knocking down” HIF1α using a gene therapy approach may protect the aging retina in diseases such as age-related macular degeneration (AMD), as this may be a useful approach to prevent the growth of abnormal blood vessels that are characteristic of the wet form of the disease.
Rafael Simó – Neuroprotection in Diabetic Retinopathy
Professor Simó from the University of Barcelona, Spain has a keen interest in exploring new treatments for diabetic retinopathy (DR). DR is an eye disease that occurs in people living with diabetes which can ultimately lead to severe loss of vision or even blindness. DR is the leading cause of blindness among working-age individuals in developed countries as well as the most common complication of diabetes.
Rafael explained that there is growing evidence to suggest that retinal neurodegeneration plays an important role in the onset of the disease. He believes that it is reasonable to propose that existing therapies that are based on protecting photoreceptor cells from degeneration may also prevent the progression of early stage DR.
Bearing this in mind, Rafael’s team have just launched a pan-European clinical trial to test the safety and effectiveness of two currently available neuroprotective drugs for the treatment of early stage DR. What is very interesting about this EUROCONDOR study is that the drugs will be administered by eye drop, as up until recently there has been a general assumption that drugs delivered by this method do not reach the back of the retina. Rafael presented some nice data to show that these drugs do indeed reach the back of the eye by simple eye drop, and this method negates the need for regular invasive injections and may have implications for other retinal degenerative conditions. The EUROCONDOR trial will begin recruiting this February in 11 sites across Europe and will conclude in 2016
John Nolan – Eye Nutrition in AMD
Professor John Nolan leads the Macular Pigment Research Group based in Waterford I.T. and has a primary interest in the role of eye nutrition for vision and the prevention of blindness. John spoke about interesting new data regarding the prevalence of age-related macular degeneration (AMD) in the Irish population that had been analysed through collaboration with The Irish LongituDinal Aging (TILDA) study in Trinity College, Dublin. This long term project aims to make Ireland the best place in the world to grow old. In this study they screened the retinas of 5000 adults over the age of 50 and based on these experiments they can estimate the prevalence of AMD in this older population in Ireland to be 7%. Prof Nolan commented “This unique data will inform Ireland, and beyond, on the seriousness of this blinding and life changing condition. It also highlights the need to put preventative measures in place before AMD becomes a larger burden on both patients and the economy.”
John’s team other big interest is in the macular pigment, the yellow substance in the middle of the retina at the back of the eye. John explained that the yellow colour is composed of three macular carotenoids; lutein, zeaxanthin and meso-zeaxanthin. Although dark green veg such as spinach, broccoli and peas are a good source of these carotenoids, Irish people generally do not consume enough of these carotenoids through diet alone. This is where supplementation has been shown to have a protective effect in relation to AMD, and the team are currently running clinical trials to determine the optimal configuration and dosage of these three important macular pigments.
Joseph Carroll – Advanced Imaging of the Human Retina
Joseph Carroll, a Professor of Ophthalmology from the Medical College of Wisconsin, United States explained that as a scientist he is fascinated by the fovea. The fovea is the central region of the macula of the retina which contains the cone photoreceptor cells and is responsible for sharp central vision, which in humans is responsible for activities such as reading and driving. Joseph said that “The fovea is a beautiful, anatomically specialised structure that we know little about in terms of how it develops and how it degenerates.” He explained that this is because a lot of the imaging techniques that are currently used do not provide images that are of a high resolution. Joseph then gave examples of how he uses the new technology of adaptive optics in order to learn more about these amazing biological structures.
Adaptive optics allows scientists and clinicians to access features of the retina that previously could not be seen. His group have demonstrated how this technology gives us a better understanding of the disease process in order to more effectively deploy treatments. He also demonstrated how this high resolution imaging will allow the identification of suitable areas of treatment in the retina, as not all patients or areas of the retina are similar. Finally, his team also believe that some of the current methods to measure the outcome of treatments are insensitive and as we begin to step into a new era of clinical trials in ophthalmology there will be a pressing need to evaluate the efficacy and outcomes of these novel therapies.
Robin Ali – Transplantation Three-Dimensional photoreceptors
Professor Robin Ali is the lead investigator of the University College London gene and cell therapy group as well as the chief scientific advisor for Fighting Blindness. Robin’s team established the world’s first gene therapy clinical trial for an inherited form of blindness back in 2007 and continues to work in this area. Robin acknowledges that gene therapy will be perhaps have the biggest impact in individuals who have surviving photoreceptor cells however stem cell therapy has the potential to be effective even when these rod and cone cells have completely degenerated.
Robin’s previous work has been focused on refining the transplantation techniques that are necessary to transplant healthy photoreceptor cells into the cells of blind mice, helping them to see again. Robin presented his latest data at this year’s conference where his team have created a “synthetic retina” grown in a lab dish based on a technique that was recently developed in Japan. This revolutionary technology allows the self-organisation of photoreceptor cells into retina-like structures within a three dimensional “jelly”. The researchers then injected roughly 200,000 of the cultured cells into living mouse retinas where they not only took root but remained present six weeks after implantation and formed the necessary neural connections to communicate visual data to the brain. Through this work, Robin and his colleagues have demonstrated for the first time that stem cells can provide a source of photoreceptors for stem retinal cell transplantation, but he cautioned that it may be many years before a clinical trial may be initiated.
James Bainbridge- RPE cell transplantation in Stargardt disease
Professor James Bainbridge is a surgeon-scientist at Moorfields Eye Hospital and University College London and is currently leading a clinical trial on behalf of the American company Advanced Cell Technology (ACT) in the UK. ACT’s treatment involves the transplantation of retinal pigment epithelial (RPE) cells derived from stem cells into the patient’s retina. The RPE cells underlie the photoreceptor cells and provide essential processes in vision such as removing waste and providing the photoreceptor cells with nourishment. In Stargardt disease, the gene mutations responsible for the condition lead to a dysfunction in the RPE and this eventually leads to the loss of photoreceptors.
James explained that a lot of evidence had been accumulated in mouse models of Stargardt disease prior to the clinical trial suggesting that these RPE cells would lend a protection to degenerating photoreceptors. He then presented some very early results from the first European clinical trial he is currently conducting which suggests that once these cells are injected they are well tolerated and crucially no safety issues have been so far recorded. His team also are measuring whether these cells survive once they are injected and for what period of time. These early phase 1/2 trials involve patients that are already severely visually impaired in order to minimise the impact of adverse effects. They will then move onto patients with better vision once the safety profile has been proven. James also concluded that for some conditions transplantation of one cell type such as the RPE or photoreceptors separately may be sufficient to stop progression of the disease, but an ambitious long term aim will be to transplant both of these cell types together.
Robert Scott-Eye Trauma and Artificial Vision
Wing Commander Professor Robert Scott is a consultant ophthalmologist at the Royal Centre for Defence Medicine, Birmingham and has helped treat the soldiers with eye injuries brought back to the UK from both the Iraqi and Afghan wars. During his years spent in warzones, he has witnessed many horrific blast injuries and has been instrumental in making combat eye protection (CEP) standard for these soldiers, a measure that has significantly reduced both secondary and tertiary blast injuries. Many of these injuries are often accompanied by deep scarring and Robert is developing the use of amniotic membrane for the prevention of scarring. One of the compounds is called decorin, and he believes that it has the potential not only to be of use in an ophthalmology setting – for example in macular degeneration and in glaucoma, but also could be used to treat burns anywhere in the body.
Unfortunately, Robert admits that saving the eyes of servicemen injured during wartime is not always possible and he has also been pioneering the use of an artificial vision system known as the BrainPort device which he helped to develop with the company Wicab. This new device essentially substitutes the other senses for sight. It translates digital information from a camera into an electrode which is placed on the tongue. The users report the sensation as pictures that are painted on the tongue with tiny bubbles which the user learns to interpret as the shape, size, location and motion of objects in their environment. Robert believes that it is better than current retinal implants in many ways because one doesn’t need to have eyes in order to use it and no surgery is required to fit the device.
We would like to sincerely thank all of our speakers and attendees who helped make Retina 2013 such a success.
Retina 2013 Public Engagement Day
This was the third consecutive year of the Public Engagement Day and this year’s event was a huge success, with an active audience of over 120 people.
The relevance of the public engagement day cannot be underestimated as a way to ensure that the members and friends of Fighting Blindness, those who are living with sight limiting conditions, are informed and have the opportunity to be involved in the issues that relate to the progress of the medical research that will enable the development of treatments for unmet medical needs. We believes that patients should absolutely be part of any discussion around health policies that will affect them, and so we work hard to facilitate discussions that will achieve that.
We had a strong turn-out at this event, it was great to meet new members and see a number of younger attendees this year also. The day included an interesting talk by Prof Tom Cotter (UCC) on the background and “story” of research, engaging our audience in the journey research takes.
An expert panel of international scientists, clinicians and patient representatives discussed some of the hot topics of the day such as the basics of how gene therapy works, the importance of patient registries as a tool for screening and the future of stem cell technologies.
A new feature to this years Public Engagement Day was the inclusion of three breakout sessions which featured a scientist and a clinician discussing particular disease areas, each group chaired by a Fighting Blindness staff member. The groups were:
- Age-related macular degeneration
- Retinitis Pigmentosa
- Inherited retinopathies
Further presentations on the day included a report on the work of the National Coalition for Vision Health and the framework strategy the group has produced. We also had a “patient empowerment” interview with one of our members, Gregor Herda, who recently walked 1,500 kilometres from Germany to Cork in aid of Fighting Blindness. Christina Fasser, president of Retina International, closed the conference with a talk entitled “Vision for the Future: Now is the Time” to highlight the importance of active participation in vision research and patient advocacy and empowerment.
We were delighted with the feedback from people who attendees at the Public Engagement Day, the breakout sessions in particular were a highlight for people, who were able to ask specific questions to experts working in the area. We are hugely grateful to everyone who contributed to the event and look forward to the next Retina Conference.