The eyes are the window to the….brain?
How the retina became a key model for brain research.
The BRAIN Initiative was launched by the National Institutes of Health (NIH), in the U.S to accelerate development of innovative technologies in order to treat neurological disorders such as Parkinson’s and Alzheimer’s disease, depression and autism. Over $1.3 billion (USD) has been awarded to researchers since 2014. Amazingly, about 40% of projects funded are vision related or involve vision health researchers. This is because when researchers want to learn about the brain they often start with the retina!
Just like the brain, the retina is made of neural tissue and is composed of different types of neurons (also called nerve cells). In addition, the retina and brain are attached via the optic nerve which transmits light signals to the brain to form images. The retina however is much more accessible and easier to study than the brain. While the neurons in the retina and brain aren’t exactly the same, studying how neurons in the retina process and transmit sensory information provides important information about how cells in the brain might function.
You can learn more about different types of experiments funded by the BRAIN initiative in an article published by the National Eye Institute (NEI), including work to identify different cell types in the brain and retina, online crowdsourcing games to map neural connections and development of visual prosthesis.
Last year, Fighting Blindness Canada (FBC) expanded our mandate to including all blinding eye diseases, knowing that advances in one disease drive innovation for vision research in general. It’s clear that this extends to other areas of research as well, including cancer, immunology and neurological or brain research. In fact many FBC funded researchers, including Dr. Phillippe Monnier and Dr. Elizabeth Simpson are also involved in research into brain function and disease in addition to their work on vision loss. It’s certainly inspiring to see how our vision researchers are not only helping to develop sight saving treatments but are helping scientists in other fields move forward!
Cholesterol lowering statin drugs may protect against diabetic retinopathy
New study suggests statins use may reduce risk of diabetic retinopathy.
A meta-analysis study, published in the European Journal of Ophthalmology last month showed that individuals who took statins were less likely to develop diabetic retinopathy. Statins are drugs that are commonly used to lower cholesterol levels. Previous studies have indicated that patients who are taking statins have reduced rates of diabetic retinopathy and are less likely to need treatment including laser treatment, anti-VEGF injections and vitrectomies than patients who aren’t taking statins. This new study analysed data from six different publications to see if the results were consistent among the different studies, patient populations, and countries. And indeed, with a combined patient population of 558,177, these results were confirmed. This is very interesting but doesn’t mean that people should just start taking statins! Like any drug, statins can cause side effects so it will be important to learn more about how statins are impacting diabetic retinopathy. For example, researchers will need to understand if statins or lowered cholesterol are directly reducing diabetic retinopathy or if patients who are on statins are more likely to be making healthy lifestyle choices or have certain favorable healthcare characteristics which may lead to better outcomes.
New treatment for AMD may reduce injection frequency
A new anti-VEGF drug expands the AMD treatment arsenal.
The discovery of anti-VEGF drugs to treat neovascular age-related macular degeneration (also called wet AMD) was a game-changer and anti-VEGF injections are now the first line therapy for the majority of patients diagnosed with wet AMD. Despite this success, some people do not respond to current treatments and the frequency of injections can put a large burden on patients and their families. Scientists and pharmaceutical companies are trying to solve these problems and there are new treatments in development in the lab and in clinical trials.
One of these, brolucizumab (Beovu®, Novartis) is an anti-VEGF injection that was recently recommended for funding by CADTH (the Canadian agency that makes recommendations about the efficacy and cost effectiveness of new drugs). In clinical trials, brolucizumab given every 12 weeks, was shown to be as effective as another anti-VEGF drug (aflibercept – Eylea®, Bayer) given every 8 weeks. Currently, CADTH is recommending that brolucizumab should only be used for patients who have not yet started anti-VEGF treatments. The next step will be for the provinces to decide if they will fund brolucizumab through the public health system.
Based on input from the community, FBC submitted a patient response to help regulators understand the experience of individuals living with wet AMD and some of the challenges they face with current treatment. Access the full CADTH recommendation. Access the FBC patient group submission.
Two new research projects from FBC-funded clinician scientists:
Oral retinoid therapy may improve vision in some patients with late-onset retinitis pigmentosa (RP).
A new study published in the journal BMJ Open Ophthalmology, shows that a 7-day treatment with a synthetic retinoid replacement (9-cis-retinyl acetate) can lead to improvements in vision which lasts up to 6 months. FBC funded researcher Dr. Robert Koenekoop (McGill University) participated in this phase 1b clinical trial which took place in Montreal and Dublin, Ireland. Patients in this trial had a rare dominant-acting mutation D477G in the RPE65 gene which leads to vision loss, usually starting in adulthood. Because of how the mutation affects the gene, this mutation cannot be treated with a gene therapy approach which can be an option for many other individuals with RPE65 mutations.
RPE65 plays an important role in producing the compounds that photoreceptors need to sense and transmit light signals. When RPE65 is mutated, these important compounds are depleted in photoreceptor cells, meaning that light signals aren’t generated, leading to vision loss. This study shows that oral retinoid therapy may help replace some of these critical compounds and could be a potential therapeutic option for individuals with this dominant acting mutation.
While this is an exciting study, it is an early phase clinical trial designed primarily to test the safety of the new therapy. Further and larger clinical trials will be important to confirm if the therapy can consistently improve vision in a safe and effective way. We look forward to hearing more in the years to come!
Novel choroideremia mutation identified in the CHM gene
Funded by FBC and published in the journal Opthalmic Genetics, Dr. Ian MacDonald (University of Alberta) has discovered a novel mutational event in the CHM gene leading to choroideremia. Choroideremia is an X-linked progressive inherited retinal disease that affects males. It is caused by a number of different mutations in a single gene, the CHM gene. There are currently no approved treatments for choroideremia, although a gene therapy is currently being tested in clinical trials.
As new treatments are being developed it is more important than ever for patients to have an accurate genetic diagnosis to find out if they are eligible for these gene-specific treatments. However, if the genetic mutation hasn’t been identified before, it may not be possible to get a genetic diagnosis, and in fact in some clinics up to 50% of patients are unable to get a genetic diagnosis. In this study, Dr. MacDonald and his team, using advanced genetic techniques, identified a previously unknown mutation event that causes choroideremia: the insertion of a “random” piece of DNA called a retrotransposon into the CHM gene, which stops the gene from working. This study is important to grow the panel of known gene mutations and increase the chance that an individual can get an accurate genetic diagnosis. Access article abstract.
The promise and challenges of innovative treatments for inherited retinal disease
This short article, from Dr. John Dowling (Harvard University) in the high impact journal Science, provides an interesting overview of different therapeutic approaches that are showing promise for inherited retinal diseases. Learn more about the promise and challenges of potential treatments such as stem cell therapy, gene therapy and retinal implant.
Finding ways to predict progression of age-related macular degeneration (AMD)
Two studies using artificial intelligence and patient reported outcomes are identifying ways to predict disease progression earlier. Learn more….
Age-related macular degeneration (AMD) is the leading cause of vision loss for Canadians over the age of 55. It occurs when the central portion of the retina, the light sensing tissue at the back of the eye, gets damaged. There are two types of AMD, dry AMD, which is more common and usually less severe and wet AMD which progresses from dry AMD and is the major cause of vision loss. It’s important to catch wet AMD as early as possible and to monitor progression closely so that it can be treated and slown down to prevent vision loss.
Two studies recently published are looking at the same question in very different ways: Can you predict when AMD will progress? The first study, published in the prestigious journal Nature Medicine, takes an artificial intelligence (AI) and deep learning approach. The UK-based team, a collaboration between scientists at the company DeepMind, University College London and Moorfields Eye Hospital, showed that a computer-based AI program was better than 5 out of 6 experts at predicting disease progression from OCT images. The second Australian study took a very different approach, investigating if there was a link between patient reported outcomes and AMD progression. The study found that patients who self-reported higher vision impairment were also at higher risk of developing wet AMD. Taken together these two studies are identifying new ways to detect AMD progression earlier and more accurately, with the aim of improving outcomes and reducing vision loss.
FBC funded researcher finds link between Vitamin D and retinal disease.
FBC Clinician Scientist Emerging Leader, Dr. Jacob Rullo from Queen’s University, has published a paper showing levels of vitamin D are higher in the eyes of patients with retinal disease, such as age-related macular degeneration and diabetic macular edema. Previous work looking at blood levels of vitamin D was inconclusive. This study shows that vitamin D is present in the eye and that it may play a role in disease progression.
Researchers turn skin cells into light-sensing eye cells
Researchers, from the University of North Texas Health Science Center have published a technique for reprogramming skin cells into light-sensing rod photoreceptors. This new technique allows researchers to skip a step in the process, and may provide a faster way to produce photoreceptors for cell replacement and stem cell therapy. When these reprogramed cells were transplanted into the eyes of blind mice, researchers detected some light under specific experimental conditions. However, this is only the first step and future experiments are required to see if the reprogrammed cells can actually restore long-term sight.
NEI researchers link age-related DNA modifications to eye disease risk
Findings point to targeting epigenome as a potential therapeutic strategy
Have you heard of the epigenome? The epigenome is all the chemical modifications or “marks” on our DNA which control which genes turn on and off. The epigenome can change in certain diseases like cancer, and now researchers at the National Eye Institute (USA) have published a study showing that it can change in the photoreceptor cells of mice as they age. Photoreceptors need energy to function and researchers found that as mice age, there were epigenetic changes that affected how their cells could use energy – demonstrating a clear link between aging, how cells use energy, and age-related eye diseases like age related macular degeneration (AMD). It might also point to a new therapeutic option: finding ways to change the epigenome to reduce vision loss.
This page is updated monthly. Visit this page next month for more exciting updates in vision research.
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