Macular Disease Foundation Australia (MDFA) has awarded more than $700,000 in research funding to six promising projects building the knowledge bank of understanding in macular disease.
The foundation said the research grants reflect the voice of the macular disease community and will answer important research questions for better treatment of macular eye diseases.
MDFA awarded three research grants worth a total of $560,000 to support three projects examining atrophic age-related macular degeneration, also known as geographic atrophy, for which there are no currently approved treatment options in Australia.
“Geographic atrophy is a significant cause of vision loss and blindness in Australia and has many unanswered research questions. One project includes a stem-cell derived modelling of geographic atrophy, and the second will address hyperspectral imaging for detecting and monitoring geographic atrophy,” MDFA said.
An additional $150,000 will fund three new early-career researchers undertaking innovative ‘blue sky’ research into macular disease, which is only possible as a result of a generous bequest made in memory of the late Faye Grant.
Their research will seek deeper insights into sight-threatening diabetic macular ischaemia, enhanced diagnostic approaches to reduce misdiagnosis of macular disease, and an evaluation of high-density lipoprotein levels that might identify people with high-risk phenotypes of age-related macular degeneration.
The function of mitochondria, the energy-producing centres in cells, are the focus of research by second-time funding recipient Dr Gerald Liew of the Westmead Institute for Medical Research, University of Sydney, and first-time recipient Dr Grace Lidgerwood of the Centre for Eye Research Australia, University of Melbourne, whose research builds upon previous research funded by MDFA.
Australia’s Governor-General Mr David Hurley presented the grants at Admiralty House in Sydney on 16 June.
“The quality of research applications was high, and they have been subjected to a rigorous assessment process based on NHMRC criteria to ensure successful projects meet the highest scientific standards,” MDFA said.
Joining MDFA’s Expert Review Panel and International Peer Reviewers in the 2023 grant selection process was its Community Review Panel comprising people caring for or living with macular disease.
MDFA CEO Dr Kathy Chapman said the inclusion of the Community Review Panel in the grant funding decision process ensures that it keeps the community living with macular disease at the centre of the work it does.
“Fourteen people joined the Community Review Panel and – like the Expert Research Panel – reviewed and weighted the value of the applications according to a set of community-specific criteria,” she said.
“The Community Review Panel helped us to understand the areas of research people with lived experience considered the most important. At the end of the process, we found the researchers and the community members were very aligned in their recommendations, which is a testament to the quality of the funded projects.”
“Our research grants program is funded through the generosity of our community, so it is very appropriate that our community has a say in how their funding is invested” Chapman said.
The latest funding round brings MDFA’s commitment to macular disease research to $5.8 million across 35 projects since 2011.
MDFA is Australia’s largest source of research funding in the field of macular disease outside of government.
MDFA Research Grants 2023
Researcher: Dr Carla Abbott
Institution: Centre for Eye Research Australia, University of Melbourne
Project title: Composition and functionality of high-density lipoprotein in age-related macular degeneration and a high-risk disease phenotype
About the project: There is currently no treatment to prevent people with early age-related macular degeneration (AMD) progressing to advanced AMD and associated vision loss. The underlying mechanisms of AMD progression is still unclear. This research study focuses on exploring the role of lipids (fatty acids) in the progression of AMD. The build-up of lipids in the retina and the metabolism (making of and breakdown) of lipids are known to be connected to AMD, as are high levels of high-density lipoproteins (HDL) in the blood. However, the exact relationship between HDLs and AMD progression is still not known. Critically, as our earlier study showed dysfunctional HDL is higher in people with AMD, the question of how effectively HDLs work to remove cholesterol from the body is now thought to be of great importance. This research aims to address this important knowledge gap and change the current thinking on the role of lipids in AMD development. It is hoped the results will pave the way for the development and rapid implementation of new treatments and therapies for AMD, some of which are already being trialled for other diseases.
Researcher: Professor Chandrakumar Balaratnasingam
Institution: Lions Eye Institute, University of Western Australia
Project title: Spatial transcriptomics in diabetic macular ischaemia
About the project: Diabetic macular ischaemia (DMI) is an important cause of severe vision loss in patients with diabetes. DMI is characterised by loss of blood vessels that are critical for supplying nutrients and removing wastes in the macula. There is currently no treatment for DMI and this is in part due to a limited understanding of the cellular pathways that are activated in DMI. In this proposal we will use human donor tissue from patients with diabetes mellitus to investigate the cellular changes that occur in DMI. The findings of this research are expected to greatly expand our knowledge regarding the cellular pathways involved in DMI and provide insights that will lead to the development of new drugs that target these pathways as a means of treating DMI. This research therefore has great bench-to-bedside translational potential and we hope to improve the quality of life in patients with diabetes by reducing visual morbidity.
Researcher: Clinical Associate Professor Gerald Liew
Institution: Westmead Institute for Medical Research, University of Sydney
Project title: Investigating mitochondrial dysfunction in macular degeneration – towards new treatments and biomarkers.
About the project: Why some people develop AMD but others do not remains somewhat mysterious. We suspect one cause of AMD might have to do with energy production in the cells of the eye, in particular problems with the mitochondria which are commonly known as the “powerhouse” of the cell. Our investigation aims to see if AMD is the result of dysfunction in the mitochondria. Our study will obtain blood samples from people with and without AMD to compare for biomarkers of mitochondrial function and examine their DNA in both the cells and mitochondria. This may help identify what molecules could be used to improve mitochondrial function, and how we can test to see which people are at high risk of developing AMD.
Grant Family Fund 2023
Researcher: Dr Grace Lidgerwood
Institution: Centre for Eye Research Australia, University of Melbourne
Project title: A stem-cell derived model of geographic atrophy age-related macular degeneration for mitochondrial-focused drug screening
About the project: It is now consensus that the cells at the very back of the retina (the retinal pigment epithelial cells or RPE) are compromised in disease. However, the exact mechanisms that cause their death is not well understood. Having access to a patient’s very own retinal cells to study in the laboratory is indeed crucial for understanding how age-related macular degeneration (AMD) and the late-stage dry form of AMD, geographic atrophy (GA) occurs, so that we can screen and develop treatments that prevent or slow progression of the disease. Induced pluripotent stem cells (iPSCs) are a powerful tool to investigate retinal diseases, as cells from patients can be converted into retinal cells to make a patient “biopsy in a dish”. Using iPSCs, we have demonstrated that we can model AMD in the laboratory. Recently, we performed an analysis of patient RPE (iPSC-RPE) using state-of-the-art scientific technology. We found that the energy powerhouses of diseased RPE, the mitochondria, do not function properly and this leads to the cells becoming stressed and functioning less efficiently. In this project, we will extend on this ground-breaking discovery by investigating clinically validated drugs that can rescue the sick mitochondria and assist them to function optimally again, to hopefully find a treatment or cure for AMD.
Researcher: Dr Alexis Ceecee Britten-Jones
Institution: University of Melbourne
Project title: Redefining macular disease diagnosis to improve access to emerging therapies
About the project: Rare inherited macular dystrophies, where macular cells die prematurely, can be misdiagnosed as the far more common age-related macular degeneration (AMD). Historically, a misdiagnosis wasn’t too problematic, as there were no treatments for either late-stage AMD or rare macular dystrophies. However, different treatments, such as gene therapy, are now being developed for both. Therefore, it is important that everyone with macular disease can be diagnosed quickly and accurately so they can receive the right treatment for their condition once these treatments are available. Further, there is currently no information for clinicians on what specific criteria they can use to differentiate rare macular dystrophies from AMD. This project aims to investigate the prevalence of macular dystrophies in people with macular disease with unusual clinical features. We will use genetic sequencing to find out how many people actually have a rare macular dystrophy and compare eye images to investigate what specific characteristics can be used to differentiate between different macular diseases. Findings will help us develop a specific set of criteria that clinicians can use to improve the diagnosis of macular diseases and ensure that every patient will receive the right treatment for their condition in the future.
Researcher: Dr Xavier Hadoux
Institution: Centre for Eye Research Australia, University of Melbourne
Project title: Evaluating the potential of hyperspectral imaging for detecting and monitoring geographic atrophy
About the project: Accurate monitoring of the sight-threatening stage of AMD, known as geographic atrophy (GA) is important to identify the people who are most likely to benefit from new treatments. Our team has discovered a new way to monitor GA. In GA, the light sensing cells of the eye, plus a key group of supporting cells, gradually die. Existing eye scans are good at detecting affected areas once these cells have died, however some types of these scans are not widely available and are not well tolerated by patients. We have developed a new eye camera that uses the same principles as sophisticated cameras that were first used by NASA to image the Earth from satellites. The camera is like a standard retinal camera, but instead of using a white flash and capturing a single photograph our camera uses a series of 30 flashes with different colours of light, capturing a photograph with each flash. Remarkably, this all happens in a quarter of a second. When these 30 images are combined, we gain incredibly detailed information about the eye. We plan to use artificial intelligence to delve into the rich information provided by these scans to see if they will provide a better way to monitor the disease, and potentially identify people who are at risk of vision loss before it happens, when treatments may be the most effective.
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