Receptor-mediated Actions Of Prorenin In Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$733,841.00
Summary
Despite improvements in patient care, the incidence of diabetic retinopathy is dramatically increasing. Recent evidence suggests that a component of a hormonal system, called prorenin, may participate in the development of diabetic organ disease. We will evaluate the role of prorenin in vascular and nerve damage in animal models of diabetic retinopathy. We will determine if a new inhibitor of prorenin, prevents retinal injury and is a potential treatment for diabetic retinopathy.
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
Translational Clinical Research In Major Eye Diseases (TCR-Eye)
Funder
National Health and Medical Research Council
Funding Amount
$2,552,355.00
Summary
The four eye diseases that cause the majority of vision loss in Australia, age-related macular degeneration, diabetic retinopathy, cataract and glaucoma, impose a significant socio-economic burden, costing our nation -$lo billion a year. This CCRE will fund a world leading, broad-based, clinical and translational research program in Melbourne and Sydney to tackle these eye diseases. The new knowledge and innovative clinical strategies developed in this CCRE will impact on clinical ophthalmology ....The four eye diseases that cause the majority of vision loss in Australia, age-related macular degeneration, diabetic retinopathy, cataract and glaucoma, impose a significant socio-economic burden, costing our nation -$lo billion a year. This CCRE will fund a world leading, broad-based, clinical and translational research program in Melbourne and Sydney to tackle these eye diseases. The new knowledge and innovative clinical strategies developed in this CCRE will impact on clinical ophthalmology and the practice of other medical disciplines.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.
The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be th ....The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be thick at the specialized area. However, in development the cells connected to the foveal photoreceptors move away from the central concentration of photoreceptors, still keeping their contacts with them. This results in thinning of the retina locally, so it has a volcanoe-like formation at the fovea, in which photoreceptors are concentrated within the crater and the displaced cells are accumulated on the rim. The events which trigger these cell displacements that form the fovea are unknown. We propose to investigate growth factors which signal between the fovea and the developing blood supply, and the relationship between the formation of the fovea and neuronal activity. This study will provide a new perspective on factors which affect central visual function and its vulnerability to insult in premature infants and in aging.Read moreRead less
Gene Based Treatment Strategies For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$2,630,000.00
Summary
Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project ....Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project aims to develop a potentially permanent solution to alleviate diabetes-related blindness in the world. The project combines several very recent scientific advances into one strategy to combat diabetic retinopathy at a molecular level. Vision is our most important sensory organ that cannot be replaced. Thus, human trials can only be conducted following extensive animal safety and efficacy trials. To date the development of new therapies has been seriously hampered by the lack of appropriate, easy to reproduce animal models for different stages of diabetic retinopathy. In addition, it aims to identify new therapeutic agents from molecules that are naturally produced by the retina while fighting the disease. Finally, tested and evaluated in the animal models. The most successful therapeutic candidates will then be further developed for human trials.If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
Retinal Vascular Signs As Predictors Of Systemic Disease Outcomes: 10-year Evolution In A Population-based Cohort
Funder
National Health and Medical Research Council
Funding Amount
$389,575.00
Summary
Recent U.S. data from two population-based studies have highlighted retinal microvascular signs as being predictive of systemic vascular and other important health outcomes in middle-aged or older individuals, particularly stroke and heart attack and mortality, independent of traditional vascular risk factors. The present application proposes to evaluate the 10-year development and progression of retinal microvascular signs and their relations to the development of stroke and other important sys ....Recent U.S. data from two population-based studies have highlighted retinal microvascular signs as being predictive of systemic vascular and other important health outcomes in middle-aged or older individuals, particularly stroke and heart attack and mortality, independent of traditional vascular risk factors. The present application proposes to evaluate the 10-year development and progression of retinal microvascular signs and their relations to the development of stroke and other important systemic health outcomes in the population-based cohort of residents attending the Blue Mountains Eye Study (BMES. Two types of retinal signs will be evaluated: firstly, the presence of specific clinical signs, such as focal narrowing of small retinal vessels (arterioles), nicking of retinal veins as arterioles cross them or presence of retinopathy (haemorrhages and other signs) secondly, measures of generalized retinal vessel calibre (narrowing) using a computer-assisted method developed for the U.S. studies. We will also develop new grading methods for two other signs. Late and will compare computer-assisted grading from 35mm slides to automated grading of vessels using a scanning device (being developed) to screen the eyes of older persons. This project builds upon our current 3-year NHMRC grant (ID153948; 2001-2003) Retinal vascular signs as risk markers for incident stroke or cerebrovascular death: A population-based assessment . In the last 2 years, this has explored different aspects of measurement and grading of these signs, has documented their relation to blood pressure and has begun to assess whether these features predict vascular events and other systemic outcomes in older Australians. The new project will assess the evolution of retinal microvascular signs over a 10-year period, using data and retinal photographs from the 10-year examinations of the BMES cohort, currently being collected, in a further current NHMRC grant (ID211069; 2002-2004).Read moreRead less