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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
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
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
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
Prorenin And The Prorenin Receptor In Diabetic Retinopathy: Involvement Of The Wnt Pathway And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$580,042.00
Summary
Diabetic retinopathy is the leading cause of blindness in people of working age. The World Health Organization predicts that by 2030 more than 300 million people will have diabetes. Given the prevalence of diabetic retinopathy and the lack of effective treatments, there is an urgent need to identify the factors that contribute to its development. This project will determine the role of components of a hormonal system, prorenin and its receptor, in diabetic retinopathy and whether they are new ta ....Diabetic retinopathy is the leading cause of blindness in people of working age. The World Health Organization predicts that by 2030 more than 300 million people will have diabetes. Given the prevalence of diabetic retinopathy and the lack of effective treatments, there is an urgent need to identify the factors that contribute to its development. This project will determine the role of components of a hormonal system, prorenin and its receptor, in diabetic retinopathy and whether they are new targets for its treatment.Read moreRead less
The Role Of The Osteoblast In Mediating Glucocorticoid-Induced Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$825,254.00
Summary
Glucocorticoids (GC) exceed most other drugs in terms of numbers of patients treated and indications. Preventing or attenuating the deleterious effects of GC on fuel metabolism is therefore of great clinical significance. Our studies will create new knowledge regarding the mechanisms of GC-induced diabetes and osteoporosis, and will contribute to the development of new approaches that are essential to tackle the pressing medical problem of GC-induced disease.
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.