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A Novel Treatment For Ameliorating Retinal Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$366,685.00
Summary
Retinal vascular disease is a leading cause of blindness and is currently treated by laser photocoagulation surgery. Although successful, this treatment is associated with serious side effects. Recently, Ellex Pty has developed a novel laser called the 2RT laser that is likely to be effective without the accompanying side effects. This study will allow examine the effect of the 2RT laser in animal models of retinal vascular disease so as to complete preclinical development of this laser.
The Significance Of Glial Dysfunction In Retinopathy Of Prematurity
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Abnormalities in cells at the back of the eye called photoreceptors are associated with at least 50% of all cases of blindness in this country.This project will determine whether substances released from dying photoreceptors cause the death of neighbouring cells. In addition we will examine whether treatments that block the actions of these released substances can prevent the death of photoreceptors, thereby providing a novel therapeutic agent for the treatment of devastating eye diseases.
Interactions Between Vasoactive, Epigenetic And Immunogenic Pathways In The Development Of Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
In our community, diabetic retinopathy is the leading cause of vision loss in people of working age. As the prevalence of diabetic retinopathy increases, there is an urgent need to understand the factors that cause its development in order to develop new treatments. This proposal will explore the contribution of hormones, the memory of retinal cells to high glucose and stress, and the immune system to diabetic retinopathy. The goal is to develop new and improved treatments for Australians.
The Role Of Renin-angiotensin And Growth Factors In Developmental And Pathological Neovascularization In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$342,562.00
Summary
In the normal retina of newborn babies, the blood vessels in the inner layers are not fully formed. These vessels are probably stimulated to grow by a reduction in retinal oxygen, which initiates the production of growth agents in retinal cells. Once the new vessels are formed the oxygen level of the retina becomes normal, and both the growth agents and blood vessel growth are reduced. A prolonged reduction in oxygen levels in the retina can have serious consequences for vision. Indeed, in some ....In the normal retina of newborn babies, the blood vessels in the inner layers are not fully formed. These vessels are probably stimulated to grow by a reduction in retinal oxygen, which initiates the production of growth agents in retinal cells. Once the new vessels are formed the oxygen level of the retina becomes normal, and both the growth agents and blood vessel growth are reduced. A prolonged reduction in oxygen levels in the retina can have serious consequences for vision. Indeed, in some eye diseases new blood vessel growth is excessive and the vessels are not properly formed, which leads to hemorrhage and ultimately blindness. Such events occur when the oxygen environment of premature babies is reduced after placement in high oxygen incubators. Also, in long-term diabetes, the oxygen levels of the retina falls as the retinal vessels become damaged. To understand the events that cause new vessel growth in retinal development and disease requires identification of the growth agents and their location in the retina. Very recently it has been found that the growth agent renin-angiotensin is made in the retina, and that its blockade in diabetic patients slows the progression of new retinal vessel growth. Renin-angiotensin is likely to cause its growth effects by increasing the production of other retinal growth agents. This proposal will study the role of renin-angiotensin and other growth agents in the developing newborn rat retina and in eye diseases. This information may lead to a further understanding of how blood vessels form in the retinas of newborn babies, and the production of new treatments for eye diseases characterized by blood vessel growth in the retina.Read moreRead less
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
Heritable Influences In Experimental Retinopathy Of Prematurity
Funder
National Health and Medical Research Council
Funding Amount
$272,591.00
Summary
Retinopathy of prematurity is an eye disease of very premature infants who require neonatal intensive care. It is a major cause of childhood blindness world-wide. Disease is caused by the growth of abnormal blood vessels in the retina, at the back of the eye. Currently, management involves the repeated examination of premature infants by an eye doctor. The babies are anaesthetized for this examination. If early disease is detected, then the affected eyes are treated with a medical laser, to burn ....Retinopathy of prematurity is an eye disease of very premature infants who require neonatal intensive care. It is a major cause of childhood blindness world-wide. Disease is caused by the growth of abnormal blood vessels in the retina, at the back of the eye. Currently, management involves the repeated examination of premature infants by an eye doctor. The babies are anaesthetized for this examination. If early disease is detected, then the affected eyes are treated with a medical laser, to burn the abnormal blood vessels. This stops the growth of these vessels and can prevent the child from going blind. However, the laser treatment itself can damage the eye. Left untreated, early retinopathy of prematurity will disappear of its own accord in some babies, but because they cannot currently be distinguished from those who will develop severe disease, all babies with signs of disease are treated. Not every premature infant develops retinopathy of prematurity: an as-yet unknown genetic factor controls susceptibility to disease. We plan to investigate this genetic basis using laboratory rats. Raised under the same conditions that are used in intensive care nurseries, baby rats develop eye disease that is similar to retinopathy of prematurity. However, as with human babies, not every baby rat develops this eye disease. We have shown a heritable tendency to retinopathy in different strains of rat. We identify the genes and proteins that differ amongst rats with or without the eye disease. We predict that identification of the inherited factors for retinopathy of prematurity in rats will provide strong clues to similar factors in humans. Our ultimate goal is to develop a test which will identify those human babies who are at risk of developing blinding retinopathy of prematurity, so that treatment is not given unnecessarily. We also expect to discover new targets for treatment.Read moreRead less
Which Oxygen Saturation Level Should We Use For Very Premature Infants? A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$2,215,600.00
Summary
Retinopathy of prematurity (ROP) is a serious complication of premature birth, and is a major cause of preventable blindness. Babies who are born before 28 weeks gestation are at greatest risk for developing severe ROP. Oxygen is one of the most common therapies used daily to care for premature babies, but high oxygen levels are one of multiple factors that can disrupt normal eye development and contribute to ROP. The current dilemma is that doctors and nurses do not know what level of oxygenati ....Retinopathy of prematurity (ROP) is a serious complication of premature birth, and is a major cause of preventable blindness. Babies who are born before 28 weeks gestation are at greatest risk for developing severe ROP. Oxygen is one of the most common therapies used daily to care for premature babies, but high oxygen levels are one of multiple factors that can disrupt normal eye development and contribute to ROP. The current dilemma is that doctors and nurses do not know what level of oxygenation is both safe and most effective for these babies. Whilst higher oxygen levels may increase ROP and other respiratory problems, it is possible that lower oxygen levels may affect other long-term outcomes. Because there is no definitive evidence regarding appropriate oxygenation, a wide spectrum of opinion and practice currently exist. Australia is conducting The Benefits of Oxygen Saturation Targeting Trial (BOOST II), a research study to solve this dilemma. BOOST II is a randomised, double blind, clinical trial, which will study the effects of using two ranges of oxygen saturation, 85-89% versus a higher range 91-95% for infants born before 28 weeks gestation. Both of these oxygen level ranges are currently used in normal practice. Patient safety will be monitored closely, and each infant will have their development, vision and health assessed by specialists at 18-24 months of age (plus the number of weeks premature), to see whether there is difference in survival free of major disability between the two groups. 1200 Australian infants will participate. This study will answer important questions about the benefits and risks of higher versus lower oxygen levels, and will improve the care of thousands of Australian children and millions more 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
Resolving 60 Years Of Uncertainty: Oxygen Saturation Targets In Preterm Infants
Funder
National Health and Medical Research Council
Funding Amount
$181,065.00
Summary
New high quality evidence has recently shown that targeting the oxygen saturation of very preterm babies at a level used routinely for many years causes an increase in their risk of death. Targeting a higher range reduces this risk but practitioners have been slow to change their practice. A program will be introduced at several newborn intensive care units which will ensure that those caring for these sick babies will be supported to move safely to a policy of higher saturation targeting.
Astrocytes And Mural Cells In The Retina: Normal Development And Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$679,616.00
Summary
The blood vessels that supply the nerve cells of the brain and retina are associated with support cells known as mural cells and astrocytes. Whereas astrocytes both ensure that the vessels do not leak and produce factors that induce vessel growth, mural cells control blood flow and are thought to promote vessel stability. We aim to characterise the development of astrocytes and mural cells as well as the interactions of these cells with blood vessels that influence vessel shape, growth, and loss ....The blood vessels that supply the nerve cells of the brain and retina are associated with support cells known as mural cells and astrocytes. Whereas astrocytes both ensure that the vessels do not leak and produce factors that induce vessel growth, mural cells control blood flow and are thought to promote vessel stability. We aim to characterise the development of astrocytes and mural cells as well as the interactions of these cells with blood vessels that influence vessel shape, growth, and loss. Aging is associated with changes in the vasculature of the central nervous system that confer a predisposition to certain conditions, such as dementia, caused by abnormal blood supply and consequent nerve cell death. We plan to investigate the contribution of astrocytes and mural cells to the vascular changes that accompany aging. These studies may lead to the development of interventions to prevent such changes and their associated pathologies. Finally, astrocyte degeneration is implicated in various neuropathological conditions, including dementia, Alzheimer's disease, and trauma. We aim to purify and characterise a population of astrocyte precursor cells whose transplantation might result in the repopulation of damaged regions of the central nervous system.Read moreRead less