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    Welcome to the UCL EyeTherapy blog

    By Prateek Buch, on 22 June 2012

    Welcome! On this blog you will find:

    Don’t forget to visit our main research website where you will find all the latest information on our work to develop novel treatments for sight loss

    Our latest posts are below – do let us know what you think!

     

     

     

    email: eye.info@ucl.ac.uk        Phone: 0207 608 7982

    UCL Institute of Ophthalmology attends SET for Britain

    By Andi M Skilton, on 21 March 2014

    Screen Shot 2014-03-21 at 15.32.25

    SET for Britain logo

    On Monday 17 March, our own Dr Anai Gonzalez-Cordero was one of the hundreds of early-career scientists in Britain invited to Westminster to present their research to Members of both Houses of Parliament (MPs) at SET for Britain.

    Dr Gonzalez-Cordero (one of 60 Biologists and Biomedical scientists in attendance) presented her work on the development of cell therapy techniques to treat vision loss, specifically the transplant of embryonic stem cell (ESC)-derived photoreceptors into the eye to replace those that have lost their normal function.

    Of the day, Dr Gonzalez-Cordero said, “It was a great pleasure to be asked to take part along with so many other talented scientists engaged in really fascinating areas of research. At UCL Institute of Ophthalmology our research into transplanting ESC-derived photoreceptors into the adult diseased retina is still in the early stage of investigation. It was very exciting to have the chance to discuss our work with important decision makers in government and help them to understand why we think these approaches, in the future, may go on to help people with severe vision loss.”

    SET for Britain is an annual event and the result of a collaboration between the Parliamentary and Scientific Committee, Society of Biology, the Royal Academy of Engineering, the Royal Society of Chemistry and the Institute of Physics. It seeks to encourage and support those at the start of their scientific career by providing a forum where scientists can present and discuss their own “ground-breaking and frontier” research with MPs.

    Prof James Bainbridge talks gene therapy for RP with The Naked Scientists

    By Andi M Skilton, on 14 March 2014

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    In this months podcast from Naked Genetics, entitled DNA Damage and Repair, Prof James Bainbridge, Department of Genetics, UCL Institute of Ophthalmology answers the monthly listener question and provides an update on the current status of research into treating retinitis pigmentosa (an inherited, degenerative eye disease that causes severe vision impairment) with gene therapy.

    Click on the player below to hear Prof Bainbridge’s answer.

    Fun and learning had by all at the BSGCT Public Engagement Day!

    By Andi M Skilton, on 14 March 2014

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    Click on image to enlarge, click back on your browser to return to this blog

    Last week, Fri 7 March, was the public engagement day of the British Society for Gene and Cell Therapy (BSGCT) at the Oxford University Museum of Natural History.

    Dr Tassos Georgiadis, UCL Institute of Ophthalmology has been on the board of the BSGCT since 2012 and chairs the public engagement sub-committee. The day provided the public with an opportunity to hear from a prestigious panel of scientists working at the forefront of gene and stem cell research as well as an opportunity for students to learn more about what it means to be a scientist.

    “The day was a great success and everyone involved has said they really enjoyed it,” said Dr Georgiadis. “We had an eminent speaker panel who were able to talk from their own experiences of working on gene and cell therapies and to dispel many of the myths and misreporting we hear everyday. The audience seemed to really appreciate a chance to learn and hear first-hand why these are such challenging and time intensive treatments to develop.”

    As well as getting to hear about cutting edge research there was the opportunity for attendees to meet, discuss and debate with scientists, patients, journalists and clinicians around the impact that research into genetic and stem cell therapies has for society.

    It was extremely engaging to watch the public as well as GCSE and A-Level students grill the speakers with some highly challenging questions around the technology and ethics behind gene and stem cell therapies. And Adam Pearson, a Patron of Genetic Disorders UK, gave a really enjoyable and honest account of his own experience of living with a genetic condition and the need to ensure that researchers and clinicians keep the person and not the disease at the forefront of their mind.

    Our congratulations go out to everyone involved, for a truly fantastic and inspiring event!

    The Department of Genetics, UCL Institute of Ophthalmology will be holding their own public engagement day on 5 July 2014 for people with age-related macular degeneration (funded by the NIHR BRC Moorfields Eye Hospital NHS Trust, the Macular Society and by a grant from the Wellcome Trust).

    You will have the opportunity to share your experiences of AMD with charities, researchers and healthcare professionals. You will hear first-hand the progress being made in world-leading research into gene and stem cell therapies for AMD and other forms of macular degeneration and have a chance to discuss the focus for future research to enable us to further support the needs and aspirations of people living with AMD.

    Check back at the end of March 2014 for information on how to register to attend.  

    After 50 years, inherited retinal disorders are now the leading cause of blindness in people of working age!

    By Andi M Skilton, on 8 March 2014

    BMJ Open logo

     

     

    Introduction to the paper

    Data published in BMJ Open, from Dr Michel Michaelides, UCL Institute of Ophthalmology, and colleagues show that ‘for the first time in at least five decades, diabetic retinopathy/maculopathy (DRM) is no longer the leading cause of certified blindness among working age adults in England and Wales, having been overtaken by inherited retinal disorders (IRDs)’.

    The authors, from the National Institute of Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Trust and UCL Institute of Ophthalmology, analysed the national database of blindness certificates of vision impairment (CVIs) in England and the Welsh equivalent (CVI-Ws), to determine the number and causes of blindness in people of working age (16 to 64 years, inclusive).

    Findings and speculations from the paper

    The report, A comparison of the causes of blindness certification in England and Wales in working age adults (16-64 year), 1999-2000 with 2009-2010’, reveals that CVIs for IRDs have risen by 4.4% (from 15.8% to 20.2%) moving from second to first position. During the same period CVIs for DRM have decreased, dropping 3.3% (from 17.7% to 14.4%), whilst optic atrophy remains the third leading cause.

    “What is clear from the findings is that inherited retinal disease should no longer be thought of as rare and not relevant,” says Dr Michaelides. “These conditions have long been, and will continue to be, an important avenue of our research. But in the future the provision of care and resources in the NHS and the allocation of research funding must be addressed if we are to tackle these conditions which now represent the commonest cause of certification in the working age population.”

    The authors speculate that it is perhaps the allocation of resources and funding seen in recent years for diabetes that has led to a subsequent decrease in CVIs for DRM. This decline is not an indication that incidence of diabetes (and subsequently incidence of DRM) are decreasing as latest data shows an increase. Likewise, incidences of IRD are not necessarily rising. Instead these findings could be attributed to the increased focus of the Government and Health Services in recent years on the treatment and management of diabetes and the effectiveness of DRM screening programmes and strategies to improve glycaemic control, among others.

    Implications of the findings from the paper

    This analysis takes into consideration only those cases which have been certified. Certification in England and Wales is by no means compulsory and many cases of vision loss go undiagnosed, misdiagnosed or unreported. However, these findings formalise the diagnostic trends that RP Fighting Blindness, a national charity funding pioneering research and support services for people with Retinitis Pigmentosa and other related conditions, have been noticing for some years.

    Whilst in terms of absolute numbers other conditions that cause severe vision loss such as age-related macular degeneration affect more people, the national impact of IRDs on the productivity of this otherwise fit and able group of working age people, as well as additional health and social costs, is huge. This is why a new focus on IRDs supported by the learnings from other diseases such as diabetes will be so important for the future.

    Taking a glimpse at our work in AMD

    By Andi M Skilton, on 28 February 2014

    As February is Age-Related Macular Degeneration (AMD) month we thought this would be an opportune moment to highlight some of the ongoing AMD research within the Gene and Cell Therapy group at the Department of Genetics at UCL Institute of Ophthalmology, as well as announce an upcoming opportunity to be more involved in shaping the future of our research.

    What is AMD?

    AMD is one of the leading causes of vision loss amongst those over the age of 50 and is caused by damage to the macula, the part of the eye responsible for central vision. Whilst vision loss isn’t total, many people with AMD are unable to see detail. As the disease progresses some people find that straight lines become distorted and the central vision of one or both eyes becomes blurred making it difficult to recognise faces, read or watch TV.

    If you or someone you know has been diagnosed with AMD your doctor is likely to have classified your condition as being one of two forms:

    • “dry” AMD – characterised by the loss of retinal pigment epithelium (RPE), the cells that nourish the light-sensitive photoreceptors found in the macular.
    • “wet” AMD – occurring in approximately 10 to 15% of people with AMD and caused by the abnormal growth of blood vessels from the choroid into the retina (a process called choroidal neovascularisation [CNV]). These new blood vessels are fragile and can leak blood behind the macula, rapidly damaging light-sensitive cells and causing sight loss.
    Diagram of the eye

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    There is no treatment for dry AMD. Existing therapies (including laser treatments, surgery and anti-VEGF injections) can delay disease progression in the wet form. These treatments do not work for everyone and can result in harmful side effects. This is why ongoing research is so important to improve the future of treatment for this major cause of sight loss.

    AMD is a multifaceted disease

    AMD has been a focus of our research for a number of years. We want to understand the pathology and biological pathways involved in AMD with the aim of identifying possible future treatment targets. Dr Ulrich Luhmann, a Senior Research Associate at the Institute, is one of several members of our team focusing on AMD.

    Dr Luhmann explains – we often think of AMD as being one disease with a wet and a dry form but the situation is much more complex. The role of VEGF in wet AMD (and other diseases) is well understood and as such it has become an established target to treat symptoms. However, there are other pathways that are responsible for AMD but the roles of these are less well understood.

    We now know that AMD is a group of disorders associated with the innate immune response, one of the bodies first defence mechanisms against infection and damage. A number of genetic factors increase our risk of developing AMD, their effect can become more pronounced as we age and in some cases further affected by external influences like smoking and diet. The aim of our research is to understand how these risk factors define a persons’ actual risk of developing AMD in order to identify novel targets for novel therapeutic strategies.

    Diagram showing the factors that define a persons risk of developing AMD

    Click image to enlarge, click back on your browser to return to the blog

    Possible future treatment strategies for AMD

    Gene and stem cell therapies are just two of the strategies under investigation here at the Department of Genetics at UCL Institute of Ophthalmology. As we learn more about how the various risk factors for AMD affect one another we hope to use this information to develop potential new treatments to prevent or reverse vision loss in AMD and other forms of macular degeneration.

    Diagram of our research approach for AMD

    Click image to enlarge, click back on your browser to return to the blog

    One such approach is gene therapy. In the future it may be possible for us to use gene therapy to target genes within the cells affected by macular degeneration and alter them to promote normal function. We are also looking at the possibility of introducing genes that encode helpful biological molecules like growth factors and antibodies. These genes would sit outside the cells where the products they encode could be produced at a higher than normal quantity to encourage normal cell function and growth or drive the removal of harmful, damaging substances from the eye.

    We are already conducting very early studies into gene therapy to treat a rare retinal disorder called Leber Congenital Amaurosis (LCA). More information on the LCA trial can be found on our website.

    For people who have sustained severe damage to the tissues of the eye, healthy cells derived from stem cells in the laboratory might be useful to replace tissues which are damaged beyond repair. Early studies into the safety of such a procedure are underway for a specific inherited form of macular degeneration called Stargardt’s disease. More information on the Stargardts trial can be found on our website.

    Our research into AMD is ongoing and we hope that our early work into gene and stem cell therapies in other diseases will help develop treatments for people with AMD in the future. More information on our work into AMD can be found on our website.

    How you can help shape the future of our AMD research

    Following on from our extremely successful Retina Patient Day in 2012 we are delighted to announce that we have received funding from The Wellcome Trust to run a similar event for people with AMD.

    On 5 July 2014 in London, UK we are running a free one-day event, endorsed by the UK Macular Society, to provide an opportunity for people with AMD to interact with charities, researchers and healthcare professionals. This is an opportunity to hear first-hand the progress being made in our world-leading research into AMD and to share your personal experiences and insights of living with this condition. With your input we will be able to ensure that our research focuses on the aspects of AMD that are most important to you.

    Watch this space – further details on how to register your interest in attending will be posted in the coming weeks.

    New Breakthrough: transplantation of photoreceptors from retina grown ‘in a dish’

    By Prateek Buch, on 22 July 2013

    Cover of Nature Biotechnology journal featuring our latest stem cell breakthroughThe UCL gene and cell therapy group, led by Professor Robin Ali, have carried out the first successful transplant of light-sensitive photoreceptor cells taken from a synthetic retina, grown ‘in a dish’ from embryonic stem cells.

    When transplanted into night-blind mice these cells appeared to develop normally, integrating into the existing retina and forming the nerve connections needed to transmit visual information to the brain.

    The findings, published today in Nature Biotechnology, suggest that embryonic stem cells could in future provide a potentially unlimited supply of healthy photoreceptors for retinal cell transplants to treat blindness in humans.

    The loss of photoreceptors – light sensitive nerve cells that line the back of the eye – is a leading cause of sight loss in degenerative eye diseases such as age-related macular degeneration, retinitis pigmentosa and diabetes-related blindness.

    There are two types of photoreceptor in the eye – rods and cones. Rod cells are especially important for seeing in the dark as they are extremely sensitive to even low levels of light.

    Previous work by our team at UCL (University College London) Institute of Ophthalmology and Moorfields Eye Hospital has shown that transplanting immature rod cells from the retinas of healthy mice into blind mice can restore their sight. However, in humans this type of therapy would not be practical for the thousands of patients in need of treatment.

    Using a new laboratory technique involving 3D culture and differentiation of mouse embryonic stem cells, which was developed recently in Japan, we were able to grow retinas containing all the different nerve cells needed for sight.

    Commenting on the latest breakthrough, Professor Ali said:

    “Over recent years scientists have become pretty good at working with stem cells and coaxing them to develop into different types of adult cells and tissues. But until recently the complex structure of the retina has proved difficult to reproduce in the lab. This is probably because the type of cell culture we were using was not able to recreate the developmental process that would happen in a normal embryo.

    “The new 3D technique more closely mimics normal development, which means we are able to pick out and purify the cells at precisely the right stage to ensure successful transplantation. The next step will be to refine this technique using human cells to enable us to start clinical trials.”

    We grew retinal precursor cells using the new 3D culture method and compared them closely with cells developed normally, looking for different markers at different stages of development. We also carried out tests to look at the genes being expressed by the two types of cells to make sure they were biologically equivalent.

    We then transplanted around 200,000 of the artificially grown cells by injecting them into the retina of night blind mice. Three weeks after transplantation the cells had moved and integrated into the recipient mouse retina and were beginning to look like normal mature rod cells. These cells were still present six weeks after transplantation. We also saw nerve connections (synapses), suggesting that the transplanted cells were able to connect with the existing retinal circuitry.

    Dr Rob Buckle, Head of Regenerative Medicine at the MRC, said:

    “Regenerative medicine holds a great deal of promise for treating degenerative diseases and the eye is one area in particular where scientists are making very rapid progress. This study is an important milestone on the road to developing a widely available cell therapy for blindness as it identifies critical steps needed to improve the success of cell transplantation and proves unequivocally that embryonic stem cells can provide a renewable source of photoreceptors that could be used to treat blindness.”

    See news items on this research:

     

    BBC: ‘Big leap’ towards curing blindness in stem cell study

    Independent: Cells to restore eyesight are grown in lab and transplanted into blind mice

    Daily Mail: Could cell transplant give sight to millions? Scientists grow retinas in the lab to create crucial connections to the brain

    Guardian:Embryonic stem cells could help restore sight to blind

    New Scientist:Eye receptor transplant promises therapy for blindness

    A new viral vector with the potential to improve eye gene therapy

    By Prateek Buch, on 28 June 2013


     

    A new type of viral vector has been developed using an innovative research technique, by researchers at the University of California, Berkeley. The new virus shows great promise as a tool for delivering genes to the eye, because it has the potential to deliver genes to the retina when injected into the gel of the eye (called the vitreous), whereas current eye gene therapy vectors have to be injected under the retina using a more invasive approach in order to reach the target cells. The new vector was reported in the media as a ‘wonder jab’ that could ‘cure blindness in 15 minutes,’ but a closer examination of its effectiveness shows there is a long way to go before such a vector could be effective in the clinic.

    While the new vector was shown to deliver genes very efficiently to the light sensitive photoreceptor cells and supporting RPE cells in the mouse eye when injected into the vitreous gel, experiments in non-human primates suggest that there might be further barriers to overcome before the new vector can be considered for use in clinical trials.

    The new virus is based on the same adeno-associated virus (AAV) that we are using in our clinical trial of gene therapy for Leber congenital amaurosis (LCA) – in this study David Schaffer and colleagues took the most commonly-used type of AAV and altered it in a number of ways. They were looking to develop a virus that would deliver genes to the light sensitive photoreceptor cells at the back of the eye after an injection into the vitreous jelly at the front of the eye.

    The approach they took was to introduce variation into the protein coat of AAV – which is what determines the type of cell the virus delivers genes to, and how efficiently it does so. They did this by introducing a random protein sequence into the virus coat, or by shuffling protein sequences with other types of AAV. The investigators injected these randomly-altered AAV particles, and a week later harvested cells that the vector had successfully delivered DNA to (which Dr. Schaffer’s team could identify as the gene being delivered was for green fluorescent protein, GFP). This allowed the team to see which of the new variants could deliver genes to cells in the eye – by repeating the process, the team identified the most efficient AAV variant. This process of directed evolution – selecting randomly-altered viruses for their ability to deliver genes to cells in the retina – produced dozens of new AAVs capable of targeting photoreceptor cells. Dr. Schaffer’s team used one variant for further testing in models of sight loss.

    The new AAV – called 7m8 –efficiently delivered DNA to all cell types in the mouse retina when injected into the vitreous gel. When engineered to deliver therapeutic genes, it also restored vision in mouse models of retinoschisis and of LCA – inherited conditions caused by mutations in the Rsh1 and RPE65 genes respectively.

    Dr. Schaffer’s team then used the new 7m8 vector in monkey eyes, to test how well it could deliver genes to a non-human primate retina following an injection into the front of the eye. Here, they saw that whilst the new virus could deliver the GFP gene to some photoreceptor cells, the vector was not nearly as efficient in monkey as in mouse. There was patchy gene delivery, suggesting that photoreceptor cells in the monkey eye, which has many features in common with the human eye, are harder to reach following injection into the vitreous gel – even when using the new type of vector.

    The aim of this research was to develop a new type of AAV – using directed evolution to generate lots of variations and selecting the best one – that could deliver genes to the retina using a less invasive approach that would be faster and less risky than the sub-retinal surgery that is currently used. Dr Schaffer’s vector appears to be the most efficient way of delivering genes to the mouse retina when injected into the vitreous, an approach that has been tried with less efficiency by other labs in previous studies. If this new vector can be further modified to be efficient in larger eyes that resemble the human eye, then it has promise for clinical application – but it is far from the ‘wonder jab’ that it was reported to be by some in the media. It is an improved tool to deliver genes, but in itself the new vector can’t be considered a treatment. We’ll need to watch this space, as further research is required to see if this tool can lead to more effective treatments.

    It’s OK to ask about clinical research – an NIHR campaign

    By Prateek Buch, on 16 May 2013

     

    We are backing a campaign run by the National Institute for Health Research (NIHR) called “It’s OK to ask,” which encourages patients to ask their doctor about clinical research.

    Clinical research is a vital tool for gathering evidence, which we can use to develop better treatments. Our group focuses on therapies for sight loss, but the process of promoting, conducting and using clinical research to improve healthcare is crucial to the whole of the NHS and to medical science in general.

    In many cases doctors will approach patients about taking part in research, but the Gene and Cell Therapy Group agrees with the NIHR that patients and carers should feel empowered to ask about clinical research too. It is crucial that as patients, we all feel confident to ask about the latest research into conditions that affect us or our friends and families, and about opportunities to participate in future studies.

    Asking your doctor or healthcare professional about research will enable you as a patient to engage with progress in medicine by staying up-to-date with the latest findings and by helping to contribute to tomorrow’s advances.

    That’s why during 2013/14 the NIHR is promoting the fact that it’s OK to ask about clinical research.

    If you have a medical condition and are undergoing treatment, they would like you to ask your family doctor, nurse or consultant about clinical research, and whether it might be right for you.

    Many of you already ask us about research into treatments for sight loss and we endeavour to provide as much information as we can about our work and how to engage with it through our website, this blog, and by directly answering your queries. In endorsing this NIHR drive for more patients to ask about research, we would like you to encourage others to do the same – there are many ways in which you can ask us about our research, including on Facebook, Twitter and by email.

    You can also let the NIHR know if you do ask your doctor about research into any condition, and what happens when you do. You can find the NIHR’s campaign on Facebook, on Twitter using #NIHRoktoask, by email or by telephone (0300 311 99 66). You could even share your story about how you got in touch with the EyeTherapy group at UCL Institute of Ophthalmology!

    We hope that through this campaign, which coincides with International Clinical Trials Day on May 20th, you feel encouraged to ask your doctor about clinical research – remember, “it’s OK to ask!”

    ‘Defining future eye research’ – a chance for you to help tackle slight loss

    By Prateek Buch, on 26 March 2013

     

    Scientific research has enhanced our understanding of the causes of sight loss, enabling the development of novel treatments. For this research to be effective, it is crucial that investigators listen to with people affected by sight loss, to help set priorities in the future direction of research. Such engagement was evident at our first Retina Patient Day last year, and we’re pleased to note a further opportunity to help shape the future of eye research – the James Lind Alliance is bringing together patients, carers and researchers to identify and prioritise the top 10 ‘unanswered questions’ relating to sight loss.

    The Alliance has set up the Sight Loss and Vision Priority Setting Partnership together with a wide range of organisations involved in tackling sight loss. This Partnership is seeking to understand your priorities for future research into eye health. In consultation with people affected by sight loss, their partners, relatives and carers and eye health professionals, the Partnership has built lists of ‘unanswered questions’ relating to many types of sight loss. You now have a chance to rank these questions in order of priority – to help shape the future direction of sight loss research.

    This vital exercise will inform groups like the Gene and Cell Therapy Group at the UCL Institute of Ophthalmology as we investigate sight loss in the future. To participate in this consultation, please visit http://www.sightlosspsp.org.uk/. There, you will find a list of different types of sight loss in the right-hand side menu. Clicking on the type of sight loss you are interested in will download a Word document with two forms, A and B. Form A is a list of ‘uncertainties,’ or unanswered questions, from which you are asked to choose ten as priorities for future research. Form B asks you to rank the questions you’ve chosen from 1 to 10 in order of priority, and has instructions on how to complete and return both Forms including deadlines for submission.

    Some important deadlines include:

    • Age-related macular degeneration (AMD) – April 12th 2013
    • Inherited retinal disease (including retinitis pigmentosa (RP), achromatopsia, Leber congenital amaurosis (LCA) and Stargardt disease) – April 15th 2013
    • Childhood-onset eye disorders (including amblyopia, coloboma and aniridia) – April 17th 2013
    • Ocular inflammatory diseases (including uveitis, birdshot retinopathy and Behçet’s disease) – March 28th 2013

    This consultation is an excellent chance for your voice to be heard by the researchers investigating causes of and treatments for sight loss – and the funding bodies that support their research. Here’s Professor James Bainbridge, leading consultant ophthalmologist at Moorfields Eye Hospital and Professor of Retinal Studies, on the importance of engaging with people affected by sight loss when setting research priorities:

    “Knowing which questions people with sight loss want answered helps us direct our research efforts into areas that will improve peoples’ lives. It is vital to engage people affected by sight loss in the design of future research to ensure that our efforts are closely directed to their needs.”

    Please return the forms to sightlossandvisionpsp@fightforsight.org.uk, and direct any enquiries regarding the consultation to Fight for Sight on 0207 264 3900.

    EyeTherapy at the Edinburgh International Science Festival – are stem cells a cure for blindness?

    By Prateek Buch, on 26 March 2013

     

    We’re really pleased that Dr. Rachael Pearson, who leads our cell therapy research team, will be presenting a talk on her research into cell therapy for sight loss at the prestigious Edinburgh International Science Festival. Dr. Pearson will discuss our pioneering work into the use of cell transplantation to repair the damage caused by retinal disease – research that shows how immature photoreceptor cells can restore vision when injected into models of inherited sight loss.

    Transplanted photoreceptor cells can integrate into the retina and can restore vision in models of sight loss

    Transplanted photoreceptor cells can integrate into the retina and can restore vision in models of sight loss

    Here’s Dr. Pearson on what she plans to present as part of one of the largest science festivals in Europe:

    “I am very much looking forward to presenting our most recent findings on developing stem cell-based therapies for the treatment of retinal degeneration and discussing these with the audience. It is a great honour to have been asked by the Royal Society to show case the research we are conducting at UCL Institute of Ophthalmology”.

    The talk takes place at the National Museum of Scotland at 5.30pm on March 27th, and is presented in association with the Royal Society.