Generation And Characterisation Of An Animal Model For Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
Age-Related Macular Degeneration (AMD) is the leading cause of irreversible blindness in the aged population in the developed world, and it is one of the least understood retinal diseases. AMD is a slow, progressive and painless condition that affects the macula, the small central part of the retina that allows one to see fine detail clearly. With the ever-increasing human life expectancy, the prevalence of AMD (15-30%) in the age group of over 75 years will significantly increase, causing enorm ....Age-Related Macular Degeneration (AMD) is the leading cause of irreversible blindness in the aged population in the developed world, and it is one of the least understood retinal diseases. AMD is a slow, progressive and painless condition that affects the macula, the small central part of the retina that allows one to see fine detail clearly. With the ever-increasing human life expectancy, the prevalence of AMD (15-30%) in the age group of over 75 years will significantly increase, causing enormous social and financial problems for the community. In spite of the significance of this problem, the exact cause of AMD is not yet known, and there is no permanent effective treatment or cure for the condition. One of the major obstacles hindering any advances towards the development of intervention strategies or therapies is the lack of an appropriate animal model. Currently, the animal models that are available for ocular diseases do not fit the human AMD situation. This project aims to characterize the first animal model for retinal degeneration caused by abnormal functioning of the retinal pigment epithelial cells (RPE). The main role of RPE cells is the phagocytosis and digestion of the continuously growing and shed light receptor segments in the eye. Their normal functioning therefore is vital to maintaining good vision. The availability of such an animal model will allow us to learn more about the changes that might occur in the eye leading to the development of AMD and to design strategies to prevent or delay progression of the condition.Read moreRead less
The Blood-Retinal Barrier - Modelling Mechanisms For Maintenance, Breakdown And Repair
Funder
National Health and Medical Research Council
Funding Amount
$394,310.00
Summary
We believe that breakdown of the barrier that separates the delicate nervous tissue of the eye from the bloodstream, the blood-retinal barrier, may be an early event in the development of age-related macular degeneration (AMD), now overall the commonest cause of blindness in Australia. We have recently demonstrated with the first scientific clinical trials to be conducted in the world that an injection of steroid into the jelly of the eye, or vitreous , of the steroid triamcinolone slows the gro ....We believe that breakdown of the barrier that separates the delicate nervous tissue of the eye from the bloodstream, the blood-retinal barrier, may be an early event in the development of age-related macular degeneration (AMD), now overall the commonest cause of blindness in Australia. We have recently demonstrated with the first scientific clinical trials to be conducted in the world that an injection of steroid into the jelly of the eye, or vitreous , of the steroid triamcinolone slows the growth of abnormal blood vessels in patients with wet AMD. In the current project, Prof Nick King, a cell biologist and viral immunologist, will collaborate with Dr Michelle Madigan, A-Prof Jan Provis, both experts in experimetnal AMD, and A-Prof Mark Gillies, a clinician-scientist specialising in AMD, to study how the treatment works using established animal and laboratory models of a damaged blood retinal barrier. We will be particularly interested in processes which are thought to critical in the development these diseases. We will also study newly described processes by which the junctions that seal the cells of the barrier together come apart. We will be interested not just in the cells that make the barrier, but also the effect of nearby cells that are thought to contribute to it. These studies will provide a solid foundation for the rationalisation of steroid treatment for AMD which can be expected to result in improved outcomes for our patients. The studies may also provide insights into how other barriers malfunction, such as the blood brain barrier which breaks down in Alzheimer s disease and multiple sclerosis.Read moreRead less
Development Of A Slit Scanning Laser Ophthalmoscope As A Screening Tool In Glaucoma Diagnostics
Funder
National Health and Medical Research Council
Funding Amount
$195,830.00
Summary
Glaucoma is typified by progressive optic disc cupping and loss of fibres with consequent characteristic field defects. Direct imaging of the retina and quantitative assessment of such images greatly increases early diagnosis of this blinding disease. The proposed device, a laser line scanning ophthalmoscope, could support non-invasive imaging to obtain 3-D information in a simple and cost effective way. This could provide objective clinical parameters to support the decision making process.
INTRARETINAL OXYGEN CONSUMPTION AND THE PREVENTION OF HYPOXIA IN RETINAL ISCHEMIA
Funder
National Health and Medical Research Council
Funding Amount
$164,444.00
Summary
Adequate oxygen supply to the retina is critical for normal visual function. The oxygen is normally supplied by the blood flowing in the two circulations that support the retina. These are the choroidal circulation, lying behind the retina, and the retinal circulation, which supports the front half of the retina. The retinal circulation is particularly vulnerable to vascular disease and insufficient blood flow (ischemia). Vascular changes are involved in a wide range of retinal diseases which ar ....Adequate oxygen supply to the retina is critical for normal visual function. The oxygen is normally supplied by the blood flowing in the two circulations that support the retina. These are the choroidal circulation, lying behind the retina, and the retinal circulation, which supports the front half of the retina. The retinal circulation is particularly vulnerable to vascular disease and insufficient blood flow (ischemia). Vascular changes are involved in a wide range of retinal diseases which are currently responsible for the majority of new blindness in our community. The choroidal circulation is relatively robust, and offers a potential avenue for increasing oxygen delivery to the retina in the clinical management of ischemic retinal diseases. The feasibility of such an approach is strongly dependent on the oxygen requirements of the retina, and how this is influenced by retinal ischemia. We plan to find out how much oxygen is consumed by the many different layers within the retina under normal conditions and then determine how this changes under ischemic conditions. We will then see if we can supply enough oxygen from the choroid by a combination of raising the oxygen content of the blood, increasing choroidal blood flow, and reducing the amount of oxygen used by the outer half of the retina. Our experiments will be done in laboratory rats, but the same principles are readily transferable to humans if they prove to be beneficial in protecting the retina from ischemic damage. Our study will also quantify the relationship between oxygen levels in the blood stream, and those in the different layers of the retina. This information may prove valuable in the treatment and the prevention of other retinal diseases where the manipulation of the intraretinal oxygen environment is an exciting new avenue of research.Read moreRead less
Advanced New Therapeutics And Diagnostics In Retinal Diseases And Glaucoma
Funder
National Health and Medical Research Council
Funding Amount
$3,550,944.00
Summary
This program proposal targets the most common blinding diseases in clinical ophthalmology. The applicant team includes research and clinical ophthalmologists and basic scientists. The team have an internationally established reputation in bringing basic science discoveries to the point where they can impact directly on clinical diagnosis and therapy. The proposed research includes new treatment therapies for diabetic retinopathy, age related macular degeneration, and retinal vascular diseases. A ....This program proposal targets the most common blinding diseases in clinical ophthalmology. The applicant team includes research and clinical ophthalmologists and basic scientists. The team have an internationally established reputation in bringing basic science discoveries to the point where they can impact directly on clinical diagnosis and therapy. The proposed research includes new treatment therapies for diabetic retinopathy, age related macular degeneration, and retinal vascular diseases. A new diagnostic technique for glaucoma and new instrumentation for detecting areas of poor blood flow and oxygen supply in the eye are also to be developed. Past successes in our current program grant make us confident that we can produce clinically useful outcomes from this new proposal.Read moreRead less
Characterising Protein And Membrane Changes In Age-related Cataract Lenses.
Funder
National Health and Medical Research Council
Funding Amount
$441,624.00
Summary
Cataract is the major cause of blindness worldwide. At present the only treatment for cataract, is surgery. This, however, is associated with complications (e.g. posterior capsule opacification), is expensive (a major component of the Health budget) and cannot keep pace with the incidence of cataract in developing nations. In addition, due to the greying of the community , this problem will be of increasing importance in the future. For prevention, we need to understand why cataract develops.
The Functional Basis Of Direction Selectivity In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
Motion is an everday visual experience, and in this project we are attempting to explain how our brains are able to detect the direction in which an object is moving. Surprisingly this is first accomplished within the retina, the light-sensitive system of neurons at the back of the eye. Thus the eyes are able to tell the brain in which direction an object is moving. So the question becomes, how do the eyes do it? We know that there is a special class of neurons, the direction-selective ganglion ....Motion is an everday visual experience, and in this project we are attempting to explain how our brains are able to detect the direction in which an object is moving. Surprisingly this is first accomplished within the retina, the light-sensitive system of neurons at the back of the eye. Thus the eyes are able to tell the brain in which direction an object is moving. So the question becomes, how do the eyes do it? We know that there is a special class of neurons, the direction-selective ganglion cells, which are able to detect the direction of image motion. The activity of these cells is increased by excitatory connections and reduced by so-called inhibitory connections. This project aims to identify the neural origin of the inhibitory connections, and discover how the excitation and inhibition work together to compute the direction of motion.Read moreRead less
I am an Opthalmologist specialising in the treatment of glaucoma and genetic eye diseases. I am trained in Molecular Genetics and researching the genetic causes of eye diseases, and how understanding the basis of disease will lead to improved outcomes.
OCULAR PERFUSION PRESSURE: A MODIFIABLE RISK FACTOR FOR GLAUCOMA?
Funder
National Health and Medical Research Council
Funding Amount
$327,560.00
Summary
This project aims to study the mechanisms underlying glaucoma, the second leading cause of vision loss. Specifically it will provide proof for the idea that a person can develop vision loss without having high eye pressure, if their blood pressure cannot provide enough supply to the eye. It will achieve this by combining expertise from several disciplines; physiology, blood pressure control, anatomy and biochemistry. This project will help to improve glaucoma detection, monitoring and treatment.