Validating A Prototype Laser System For Intraocular Surgery
Funder
National Health and Medical Research Council
Funding Amount
$495,551.00
Summary
Intraocular surgery is a vital tool for treating common sight threatening diseases such as proliferative diabetic retinopathy and retinal vein occlusion. We seek to develop a prototype laser system to replace currently used mechanical instruments. We have demonstrated that UV laser ablation can afford much greater precision. Laser parameters for the new system will be optimised based on our previous achievements. The new system will be tested in animal trials and clinically.
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
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
A Novel Ionic Current Contributing To Spasm Of Small Blood Vessels
Funder
National Health and Medical Research Council
Funding Amount
$287,500.00
Summary
Vascular smooth muscle can produce strong constrictions or spasms that can severely limit blood flow. Disorders arising from such spasms include sudden death, neurological deficits, visual and hearing loss or impairment, Raynaud's phenomenon (painful episodic contraction of the fingers and toes) and intestinal necrosis. Common mechanisms are likely to underlie the spasms associated with these disparate disorders. In a recent electrophysiological study of vascular smooth muscle, we discovered a n ....Vascular smooth muscle can produce strong constrictions or spasms that can severely limit blood flow. Disorders arising from such spasms include sudden death, neurological deficits, visual and hearing loss or impairment, Raynaud's phenomenon (painful episodic contraction of the fingers and toes) and intestinal necrosis. Common mechanisms are likely to underlie the spasms associated with these disparate disorders. In a recent electrophysiological study of vascular smooth muscle, we discovered a novel membrane current which we refer to as the plateau current. This current has a strong depolarizing influence that is likely to make a major contribution to the spasms, particularly in arterioles and small arteries which are more dependent on depolarization for contraction. Block of this current is expected to minimize the depolarization and therefore prevent or ameliorate spasm of the vessels. Thus the plateau current represents a new field of therapeutic potential for addressing vascular problems that have significant health implications. However, therapeutic manipulation of the current requires knowledge of its properties. In this project we will determine the biophysical and pharmacological properties of this current using voltage-clamp techniques. We will then use this information to assess its functional significance by recording membrane potential with intracellular microelectrodes simultaneously with contractile activity. We will also compare small vessels obtained from volunteers with or without the vasospastic disorder of Raynaud's phenomenon. Our previous work using these techniques was described in J Physiol as a microelectrode, patch clamp and myograph study of the highest quality and of supreme technical difficulty and scored a Top-Ten hit rate. Since we are the only ones to record the plateau current, we are in a unique position to make significant progress to our understanding of contraction, including spasm, in small blood vessels.Read moreRead less
RCT Of Aspirin And Fish Oil For The Prevention Of Thrombosis In Arterio-venous Fistulae For Dialysis Access
Funder
National Health and Medical Research Council
Funding Amount
$1,869,190.00
Summary
This randomised, placebo-controlled clinical trial aims to determine whether the anti-platelet agents aspirin and fish oil, either alone or in combination, will effectively reduce the risk of early thrombosis (blood clots) in arterio-venous fistulae (AVF) that are used for accessing the circulatory system in dialysis. The trial is to be conducted by the Australasian Kidney Trials Network (AKTN). 1200 patients requiring haemodialysis who are scheduled to undergo creation of an AVF and are not cur ....This randomised, placebo-controlled clinical trial aims to determine whether the anti-platelet agents aspirin and fish oil, either alone or in combination, will effectively reduce the risk of early thrombosis (blood clots) in arterio-venous fistulae (AVF) that are used for accessing the circulatory system in dialysis. The trial is to be conducted by the Australasian Kidney Trials Network (AKTN). 1200 patients requiring haemodialysis who are scheduled to undergo creation of an AVF and are not currently taking anti-platelet agents will be recruited over 3 years. AVF is the accepted standard for haemodialysis patients because it utilises the patient's own artery and vein to allow repeated access to the vascular system with a minimal risk of complications. Failure of the AVF means the use of inferior permanent venous catheters or arterio-venous artificial grafts. These devices are more costly to insert, and have an increased risk of failure due to infection and thrombosis. Reducing this rate of failure by simple, cheap and readily available interventions has the potential to reduce these problems. Aspirin has been chosen because of its well-established anti-thrombosis effects. Fish oil has a number of biological effects which make it an attractive agent for the prevention of vascular access thrombosis. Study treatment will be aspirin 100 mg per day or matching placebo, and fish oil 4 gm daily or matching placebo, both commencing on the day prior to surgery and continued for 3 months. If the trial demonstrates a positive effect of either or both agents, this will lead to a reduction in thromboses, quicker time to working dialysis access, and less need for surgery.Read moreRead less
Development Of Platelet-Targeted Nanoparticles For Magnetic Resonance Imaging Towards The Detection Of Thrombi/Emboli And Vulnerable Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$606,524.00
Summary
Heart attack, stroke and pulmonary embolism typically strike without warning and either kill patients or cause devastating disabilities. Currently, we do not have diagnostic methods to identify patients and the blood vessels at risk. We have developed a new innovative MRI nanoparticle directed against activated platelets for the detection of _at risk� blood vessels. The current funding is requested to optimise the manufacture of this targeted MRI nanoparticle and to undertake the animal studies ....Heart attack, stroke and pulmonary embolism typically strike without warning and either kill patients or cause devastating disabilities. Currently, we do not have diagnostic methods to identify patients and the blood vessels at risk. We have developed a new innovative MRI nanoparticle directed against activated platelets for the detection of _at risk� blood vessels. The current funding is requested to optimise the manufacture of this targeted MRI nanoparticle and to undertake the animal studies required to enter early stage clinical trials.Read moreRead less
Modulating Retinal Glutamate Transport In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the m ....Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the mechanisms that regulate the concentration of glutamate in the retina. If these mechanisms could be made to work more efficiently, they may prevent the build-up of the glutamate and therefore prevent damage to the nerve cells. Understanding these mechanisms will aid in the development of an effective treatment to prevent blindness when there is a blockage of the blood supply to the retina.Read moreRead less
Characterisation Of MiRNAs That Regulate Vascular Leakage.
Funder
National Health and Medical Research Council
Funding Amount
$167,493.00
Summary
Vascular permeability or leak is a major problem in diseases such as cancer and in cardiovascular diseases . MicroRNAs (miRNAs) are small control genes that influence dveleopment and disease. We have identified a miRNA cluster in endothelial cells, the cells that line the blood vessels, that is important in the control of vascular leak. This project is focused on understanding the impact of these miRNAs in disease.