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
Defining Vascular Health And Modifiable Risk Factors Over Time In Childhood.
Funder
National Health and Medical Research Council
Funding Amount
$368,061.00
Summary
Adult heart disease and strokes have their origin in childhood. We will follow healthy children and children with diabetes or obesity over 2 years during puberty when blood vessel disease is detectable. We will define which are the most sensitive markers of blood vessel disease and the continuum of risk factors. This is essential knowledge to best define children at risk and to test clinical and public health interventions.
The Fremantle Diabetes Study Phase II: A Community-based Study Of Diabetes Care, Control, Complications And Cost
Funder
National Health and Medical Research Council
Funding Amount
$1,307,780.00
Summary
In Phase I of the Fremantle Diabetes Study (FDS), valuable and detailed data on a wide range of subjects were obtained from a community-based patient cohort between 1993 and 2001. There is a large body of evidence that the nature and treatment of diabetes in Australia is changing rapidly. In order to provide up to date information to health care providers and government agencies, to confirm observations made in FDS I and to venture into new research areas, Phase II will be conducted.
Aldosterone Inhibition And Diabetic Retinopathy: Treatments And Mechanisms Of Action
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The World Health Organization predicts that by 2030, more than 360 million people will have diabetes. Despite almost all patients developing retinopathy, current treatments do not prevent disease progression. One strategy being evaluated is blockade of a hormone called angiotensin II. We have new evidence that a related system called aldosterone exists in retina and contributes to damage. This project will determine if aldosterone blockade is a potential treatment for diabetic retinopathy.
Characterisation Of Novel AGE Binding Proteins: Implications For Diabetic Vascular Complications.
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This i ....This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This is a highly novel finding which now needs to be examined in more detail. The ERM proteins which include ezrin, radixin and moiesin are found at many sites of diabetic complications including the kidney, retina and blood vessel wall. They have a number of functions including effects on cell adhesion and cell structure. This is important in diabetes where changes in cells including altered structure have been observed. This grant will characterise the interactions between AGEs and ERM proteins at the molecular and cellular level. It will define how AGEs influence cells via interactions with ERM proteins. These studies have the potential to lead to treatments that may modulate the AGE-ERM interactions, thereby retarding or preventing diabetic vascular complications. These complications are of important clinical significance since they are the major cause of morbidity and mortality in the diabetic population. Furthermore, diabetes is a major cause of premature atherosclerosis in our community, diabetic kidney disease is the leading cause of end-stage renal failure in the Western world and diabetic retinopathy (eye disease) is the main cause of blindness in the working age population.Read moreRead less
Hormonal Predictors Of Cardiovascular Outcomes And Mortality In Ageing Men: The Role Of Androgens And The IGF System.
Funder
National Health and Medical Research Council
Funding Amount
$125,035.00
Summary
As men age levels of testosterone and growth hormone fall while ill health increases. We do not know if low hormone levels directly cause heart disease. We will measure testosterone and IGF1, which reflects growth hormone, in 4,200 older men, and relate hormone levels to the future risk of ill health especially heart disease, stroke and large artery blockages. This will clarify whether low hormone levels increase risk of ill health, and the value of studies to test hormone therapy in older men.
Genetic And Metabolic Determinants Of Spontaneous Physical Activity
Funder
National Health and Medical Research Council
Funding Amount
$67,828.00
Summary
It could be argued that obesity is the most significant public health problem facing Australians today. Almost one in five adult Australians are obese, making them highly susceptible to diabetes, coronary heart disease, high blood pressure, high blood lipid levels, and some cancers, as well as reduced psychosocial health. There is therefore an urgent need to reduce the prevalence of obesity in our society. Unfortunately, attempts to sustain significant weight loss by dieting and exercise are nea ....It could be argued that obesity is the most significant public health problem facing Australians today. Almost one in five adult Australians are obese, making them highly susceptible to diabetes, coronary heart disease, high blood pressure, high blood lipid levels, and some cancers, as well as reduced psychosocial health. There is therefore an urgent need to reduce the prevalence of obesity in our society. Unfortunately, attempts to sustain significant weight loss by dieting and exercise are nearly always unsuccessful and none of the anti-obesity drugs currently on the market are safe to use long-term. Effective treatments for obesity are only likely to be developed once we understand more about what controls body weight regulation. An inactive lifestyle is clearly a risk factor for obesity. Spontaneous physical activity (or activity associated with daily life, as opposed to formal exercise) can play a major role in determining body weight. Recent work suggests that spontaneous physical activity is influenced not only by our environment but by our biological makeup as well (i.e. genetic and metabolic factors). The aim of this study is to investigate what some of these factors are, and whether they are responsible for altering body weight regulation in animal models of obesity. Specifically we will be looking at whether spontaneous physical activity is influenced by circulating hormones (such as leptin, oestrogen, and pancreatic polypeptide) and a messenger molecule (nitric oxide), and we will also identify genes which influence physical activity in a mouse model of obesity. By examining the genetic and metabolic basis of inactivity in obese rodent models, this project will further our understanding of how energy balance is disturbed in obesity in the hope of developing better therapies to treat obesity in the future.Read moreRead less
Microvascular Complications Of Diabetes - Potential Role Of Regenerative Therapies
Funder
National Health and Medical Research Council
Funding Amount
$32,003.00
Summary
The global burden of diabetes is projected to reach more than 366 million by 2025. According to the AusDiab 2005 study, each year 0.8% of Australians develop diabetes. Diabetes is the leading cause of end-stage kidney disease in Australia. Current treatments slow damage to the kidney, but do not reverse kidney damage. We will explore the potential for adult progenitor cells (endothelial progenitor cells) to reverse damage to the kidney and restore its function.