A Longitudinal Study Of Nerve Morphology In Diabetic Neuropathy Using Novel Non-invasive Ophthalmic Surrogate Markers
Funder
National Health and Medical Research Council
Funding Amount
$540,372.00
Summary
This research project will use two new ophthalmic instruments - the corneal confocal microscope and non-contact corneal aesthesiometer - to directly monitor changes in corneal nerves and corneal sensitivity, over a 5 year period, in diabetic patients suffering from a painful condition of the arms and legs known as diabetic neuropathy. This study will generate important new information that could allow diabetic doctors to more accurately monitor the progression of the disease.
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
A Novel Mechanism For Manipulation Of Peripheral Glucose Utilization In Patients With Type 2 Diabetes Mellitus.
Funder
National Health and Medical Research Council
Funding Amount
$283,500.00
Summary
Significance: Over 600,000 Australians have type 2 diabetes (approximately half are undiagnosed) and it is estimated that this number will increase substantially to 10% of the adult population over the next 10 years. At the conclusion of this grant we expect to understand whether specific signalling molecules might plausibly represent the basis of a novel therapeutic approach to control blood glucose. If successful, this work could contribute to improved metabolic control and prevention of diabe ....Significance: Over 600,000 Australians have type 2 diabetes (approximately half are undiagnosed) and it is estimated that this number will increase substantially to 10% of the adult population over the next 10 years. At the conclusion of this grant we expect to understand whether specific signalling molecules might plausibly represent the basis of a novel therapeutic approach to control blood glucose. If successful, this work could contribute to improved metabolic control and prevention of diabetic complications through new blood glucose lowering agents. Hypotheses: Muscle is the major site of glucose disposal in the body and the two most relevant stimuli for glucose uptake into muscle are insulin and muscle contraction (exercise). The insulin pathway is impaired in patients with type 2 diabetes leading to high blood glucose and complications. Glucose uptake in response to exercise however appears to be normal in patients with type 2 diabetes. Indeed we have evidence to suggest that this pathway may compensate for impaired insulin action in type 2 diabetes. We hypothesise that molecules activated by contraction (exercise) may be useful as therapies to improve resting glucose control in type 2 diabetic patients. Aims: We plan a series of three studies to examine whether glucose uptake may be improved both acutely and chronically at rest by an agent implicated in exercise mediated glucose uptake.Read moreRead less