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Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
Using New Retinal Imaging Technologies To Improve Treatment And Classification Of Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$227,644.00
Summary
Diabetic retinopathy is the leading cause of blindness in Australia. This project aims to use new ways of imaging changes in the back of the eye to try to improve the treatment and diagnosis of diabetic retinopathy.
Do Postjunctional Alterations Explain The Effects Of Diabetes On Neurovascular Transmission?
Funder
National Health and Medical Research Council
Funding Amount
$390,886.00
Summary
Diabetes produces disordered skin blood flow that increases risk of skin ulcers and gangrene. The project investigates nervous control of skin blood vessels in diabetes. It is assumed that all affects of diabetes on nerve function are explained by loss of nerves. We hypothesize that some affects of diabetes are due to dysfunction of blood vessels and not to nerve loss. The objective is to identify drug targets to improve blood flow in skin and thereby reduce the risk of skin ulcers and gangrene.
Vascular And Neuro-glial Dysfunction In Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
The retina is responsible for sight. Vision occurs by interactions between blood vessels, neurons (cells that transmit electrical signals for vision) and glia (cells that support the retina). In diabetes, high amounts of glucose in blood increases certain factors within retinal cells. These factors slowly cause damage, such that after 15 years of diabetes all patients will have some retinal disease and many will loose sight. Indeed, diabetes is the leading cause of blindness in working people. T ....The retina is responsible for sight. Vision occurs by interactions between blood vessels, neurons (cells that transmit electrical signals for vision) and glia (cells that support the retina). In diabetes, high amounts of glucose in blood increases certain factors within retinal cells. These factors slowly cause damage, such that after 15 years of diabetes all patients will have some retinal disease and many will loose sight. Indeed, diabetes is the leading cause of blindness in working people. The main treatment for diabetic retinal disease is to burn away damaged blood vessels, however, this treatment has problems. Firstly, the burns destroy healthy retina and the disease continues, secondly, the treatment is performed late in the disease and therefore does not prevent the early changes in retinal cells, and thirdly, changes in neurons and glia are often not considered. Therefore, there is an urgent need to understand how blood vessels, neurons and glia interact with each other to threaten vision in diabetes, with the intention of developing safer and more effective treatments. This will be the focus of the current project. Currently, there are no studies that have examined the sequential changes in retinal blood vessels, neurons and glia in diabetes. This is mainly due to the lack of an experimental rodent model that progresses from mild to severe diabetic retinal disease. In 2003, we established such a model in the diabetic Ren-2 rat. In this project the diabetic Ren-2 rat will be used to study retinal cell changes and also to identify the factors that damage these cells. We suggest that angiotensin, bradykinin and VEGF are involved. These factors are present in the normal retina and are increased in diabetes. We will block these factors with specific drugs with the intention of understanding how these factors affect retinal cells in diabetes, and also to develop new drug therapies for the treatment of both early and late diabetic retinal disease.Read moreRead less
My research focuses on the mechanisms responsible for diabetic kidney and heart complications with an emphasis on identifying novel targets as the basis for developing new treatment to reduce the burden of these complications. It is hypothesised that diabetic complications arise as a result of a number of key factors, the most important being chronic elevation of blood glucose.
Role Of Epigenetic Mechanisms In Diabetic Vascular Complications
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called ox ....Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called oxidation pathways, interferes with enzymes which affect the structure of DNA and related molecules resulting in altered expression of many proteins. One of these proteins known as NF kappa B is activated in diabetes, probably by mechanisms involving regulation of these enzymes which play a central role in modifying gene structure. By clarifying the exact mechanisms at a molecular level that mediate the effect of glucose on genes and proteins it will be possible to target these molecules and develop new treatments to prevent, retard or reverse the blood vessel complications that are so common in diabetes.Read moreRead less
Role Of Chromatin Remodelling In Diabetic Renal And Vascular Complications: In Vivo Studies
Funder
National Health and Medical Research Council
Funding Amount
$474,618.00
Summary
Even after diabetics return to improved blood glucose levels after a period of poor blood glucose control, the kidney and blood vessel complications progress. The cause of this metabolic memory remains unexplained. This proposal focuses on sustained changes as a result of prior glucose levels in proteins called histones that are part of the wrapping of DNA. Using a new technique called carrier ChIP we will study histone modifications in the blood vessels and kidneys in diabetes.
Angiotensin II AT2 Receptor In Diabetic Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$477,472.00
Summary
Activation of the angiotensin 2 receptor may have effects leading to large artery disease in diabetes. We will investigate the role of the AT2 receptor in diabetes using knockout animals, novel blockers and activators and most importantly the role of the AT2 receptor in macrophages in diabetes.
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.