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
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
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.
New Dynamometric Techniques For Predicting Glaucoma Progression
Funder
National Health and Medical Research Council
Funding Amount
$171,825.00
Summary
Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and ....Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and progression of glaucoma. This is a major breakthrough because there is no other means of predicting in which glaucoma patients vision loss will develop most rapidly. This information will be very helpful in deciding which patients should have the most agressive treatment to restore normal intraocular pressure. This project seeks to develop a new commercial device to make such an examination easy for any clinical ophthalmologist. The device allows the doctor to examine the vessels at the disk whilst applying slight pressure to the eye to temporarily raise intraocular pressure. A footswitch is pressed when the doctor sees the vessels pulsate. The required force is recorded by a laptop computer and the data stored along with the patients details. Now we have confirmed the ability of such a measurement to predict the rate of visual field loss in glaucoma, such a measurement will become much more widespread in clinical ophthalmology, offering a new and large scale opportunity for such instrumentation. Our device will be easy to operate, more comfortable for the patient, and will be of major diagnostic value in glaucoma clinics worldwide.Read moreRead less
Functional Recovery From Retinal Degeneration: Genetic, Environmental And Senescent Models
Funder
National Health and Medical Research Council
Funding Amount
$265,888.00
Summary
This project is directed towards treatment for the blindness caused by retinal degeneration. The retina of the eye degenerates in several groups of diseases, and from several causes. Many cases affect young people and result from small genetic mutations in key proteins. Many appear to be caused by environmental damage to the retina, perhaps at birth. Retinal degeneration causes progressive blindness in a minority of younger people (about 1 in 4,000, so 5,000 Australians and 1-2 million people wo ....This project is directed towards treatment for the blindness caused by retinal degeneration. The retina of the eye degenerates in several groups of diseases, and from several causes. Many cases affect young people and result from small genetic mutations in key proteins. Many appear to be caused by environmental damage to the retina, perhaps at birth. Retinal degeneration causes progressive blindness in a minority of younger people (about 1 in 4,000, so 5,000 Australians and 1-2 million people world-wide). This condition is known as Retinitis pigmentosa. However, the normal retinal undergoes a slow loss of photoreceptors whose effect is cumulative, so that the vision of all peoples slowly fades towards the blindness of old age. In this form, retinal degeneration affects potentially everyone. We have recently published an 'oxygen toxicity' theory of retinal degeneration to account for both retinitis pigmentosa and senescent degeneration. The theory applies whether the dystrophy is preciptated by genetic mutation or by environmental factors . By the time a person becomes aware of blindness (commonly night blindness) from retinal degeneration, the loss of vision results (it is argued) from 2 causes: the death of some photoreceptors (the retinal cells which detect light) and damage to surviving photoreceptors. Both death and damage are caused by oxygen toxicity, arising from particular features of the retina's metabolism and blood supply. Further, the relentless progression of the blindness is inherent in the mechanisms of oxygen toxicity. In preliminary work we have been able to slow retinal degenerations and, importantly, to restore function in degenerating retinas by countering the oxygen toxicity. Experiments are proposed to expand this evidence and explore the time course, permanence and generality of these effects. The tests of retinal recovery and stability, and the mechanisms of countering oxygen toxicity will be readily applicable to clinical trials.Read moreRead less
Characterizing Novel Therapeutic Interventions In A New Model Of Focal Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$536,794.00
Summary
Focal retinopathies such as age-related macular degeneration pose an immense burden on our society, both socially and economically. We have recently developed an animal model that allows us to investigate for the first time, drugs and therapies that might be used to treat AMD both after its onset, and more significantly, in at-risk populations before onset of the disease.
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