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How Does Glucose Protect The Retina And Optic Nerve Against Ischaemia?
Funder
National Health and Medical Research Council
Funding Amount
$418,171.00
Summary
Raised blood sugar levels are generally considered to be bad for nerve cells, especially those in the eye. But we have made a groundbreaking discovery finding that in the short-term, sugar can rescue nerve cells in the eye from death caused by lack of blood flow. In this project we will investigate how this remarkable effect is achieved.
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
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.
Measurement And Prognostic Significance Of Retinal Vessel Parameters In Childhood
Funder
National Health and Medical Research Council
Funding Amount
$264,175.00
Summary
We propose that structural micro-vessel changes associated with blood pressure develop early in childhood and that these may predict future cardiovascular risk in adulthood. In order to address this important issue, we will measure retinal vascular diameter and other microvascular signs from retinal photographs taken of a large population-based sample of Sydney schoolchildren (n-4,093) during 2003-2005. This project included 1740 6-year olds and 2353 12-year olds from 52 schools across Sydney. A ....We propose that structural micro-vessel changes associated with blood pressure develop early in childhood and that these may predict future cardiovascular risk in adulthood. In order to address this important issue, we will measure retinal vascular diameter and other microvascular signs from retinal photographs taken of a large population-based sample of Sydney schoolchildren (n-4,093) during 2003-2005. This project included 1740 6-year olds and 2353 12-year olds from 52 schools across Sydney. Almost all had photos taken. We will test the hypothesis that retinal arteriolar calibre in children is strongly influenced by ambient (current) blood pressure, after accounting for confounding influences of image magnification (eye shape , size and refraction) and size of the child (body mass). We also predict that familial, eye and general health factors also determe diameter of retinal vessels, and will account for these in the analysis. We will test the notion that certain retinal vessel branches or trunks will be more affected by blood pressure variability than others. This finding, if shown, could improve our understanding of retinal micro-vessel signs in older adult populations and may assist developments of rapid image scanning to assess vessel diameter. In a pilot study grading retinal vessel diameters from one eye of a random sample of the 6-year old images, we found that increasing blood pressure was strongly associated with slightly narrower retinal arterioles. Though modest in magnitude, this effect was highly significant and was independent of other factors found to determine retinal vessel diameter. Evidence is emerging that cardiovascular disease may be linked to BP levels in early life. It seems possible that retinal micro-vessel changes in children may also predict future cardiovascular risk in adulthood. This research will evaluate measures to study the long-term effects of variations in blood pressure and its genesis in childhood.Read moreRead less
Retinal Microvascular Signs In Acute Stroke: Prognostic Significance And Relevance To Underlying Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$375,425.00
Summary
This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that asses ....This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that assess size of the small retinal arteries compared to veins (the arteriole-to-venule ratio) and will document other abnormalities, such as microaneurysms, haemorrhages, tortuosity and focal and generalised vessel narrowing and wall opacity. In normal populations these signs are associated with hypertension, inflammation and endothelial dysfunction and predict future stroke. These signs, and their significance have not been systematically studied in acute stroke. This may offer a window into the brain for important subgroups of stroke such as lacunar stroke. It is increasingly hard (and remains technically very difficult) to study the cause of lacunar stroke, affecting 10,000 Australians each year, as lacunar stroke has a lower fatality rate (and thus few opportunities for post mortem studies) but a high disability rate. Lacunar stroke is known to be due to small vessel disease but the exact nature of this disease is unknown. Echocardiography (to identify heart and major blood vessel abnormalities) and carotid duplex scanning (to identify critical stenosis of the major blood supply to the brain) are commonly normal in this type of stroke, and brain scanning with computerised tomography (CT) or magnetic resonance (MR) merely shows the outcome of the small vessel disease. The eye develops as part of the brain and thus retinal vascular abnormalities could add important knowledge to our understanding of stroke and add clinically useful data in the assessment of patients with stroke.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
Retinal Microvascular Signs In Angina And Coronary Artery Disease: The Australian Heart Eye Study (AHES)
Funder
National Health and Medical Research Council
Funding Amount
$631,223.00
Summary
The Australian Heart Eye Study will determine whether vessel signs from the retina at the back of the eye are an independent marker of heart disease as assessed by a coronary angiogram. New imaging techniques permit a rapid assessment of these signs. This project could lead to the development of an innovative, non-invasive test that could be used to screen people for the risk of coronary heart disease, in addition to traditional risk factors like blood pressure, smoking, cholesterol and obesity.
Glial-neuronal-vascular Interactions In A Novel Transgenic Model Of Muller Cell Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$626,585.00
Summary
Muller cell disfunction is a feature shared by many retinal diseases. This project aims to study the contribution of Muller cell dysfunction to retinal neuronal damage and blood-retinal barrier breakdown in a novel transgenic model we recently generated. Results of this study will also be of interest to scientists and clinicians seeking to understand better and treat diseases of the central nervous system in general.