Modulating Retinal Glutamate Transport In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the m ....Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the mechanisms that regulate the concentration of glutamate in the retina. If these mechanisms could be made to work more efficiently, they may prevent the build-up of the glutamate and therefore prevent damage to the nerve cells. Understanding these mechanisms will aid in the development of an effective treatment to prevent blindness when there is a blockage of the blood supply to the retina.Read moreRead less
The Structural Basis Of Direction Selectivity In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$401,705.00
Summary
The retina is part of the central nervous system and there are almost one hundred types of retinal neurons which process visual information before it is passed up the optic nerve to the brain. This project examines how some of these neurons are wired together to form a simple neuronal circuit that detects the direction of a moving object. The elucidation of the cellular mechanisms of direction selectivity will provide an important paradigm of complex processing by simple neuronal circuits, with ....The retina is part of the central nervous system and there are almost one hundred types of retinal neurons which process visual information before it is passed up the optic nerve to the brain. This project examines how some of these neurons are wired together to form a simple neuronal circuit that detects the direction of a moving object. The elucidation of the cellular mechanisms of direction selectivity will provide an important paradigm of complex processing by simple neuronal circuits, with direct relevance to information processing in other parts of the central nervous system. In particular, the project may provide strong evidence for two neuronal strategies that may be of general significance. First, information may be processed at a very local level, which would greatly increase the computational power of a single neuron. Second, neurons may make selective contact with only some processes of an input neuron, which would require novel mechanisms for producing the necessary specificity.Read moreRead less
Electroretinogram Recordings Of Human Scotopic Dark Adaptation Following Intense Bleaching Exposures
Funder
National Health and Medical Research Council
Funding Amount
$272,250.00
Summary
After a human subject has been exposed to intense illumination, it can take many minutes for the eye to regain full sensitivity, as one experiences (for example) when entering a dark cave after being out on a bright sunny beach. This project will investigate the processes that occur in the cells of retina lining the back of the eye, that prevent the instantaneous recovery of vision following intense illumination. Electrical recordings will be made from the eyes of normal individuals, using new t ....After a human subject has been exposed to intense illumination, it can take many minutes for the eye to regain full sensitivity, as one experiences (for example) when entering a dark cave after being out on a bright sunny beach. This project will investigate the processes that occur in the cells of retina lining the back of the eye, that prevent the instantaneous recovery of vision following intense illumination. Electrical recordings will be made from the eyes of normal individuals, using new techniques that allow the activity of different types of nerve cell in the retina to be monitored. The study will determine how it is that events in the light-detector cells of the eye (the rod and cone photoreceptors) influence the activity of subsequent nerve cells in the visual system, and how these events contribute to the poor vision that one experiences following bright lights.Read moreRead less
I am a neuroscientist interested in injury to the nervous system with emphasis on promoting functional recovery and clinical translation. Injury models are neurotrauma, the long-term effects of maternal drug administration on offspring and diabetic retino
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.
TRAFFICKING OF METABOLITES BETWEEN M LLER CELLS AND NEURONS IN DIABETIC RETINOPATHY.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Diabetes is the leading cause of blindness in the working population. In some diabetics, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an incease in growth factors from cells in the retina called Muller cells. Muller cells are vital for the normal function of the retina, and a ....Diabetes is the leading cause of blindness in the working population. In some diabetics, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an incease in growth factors from cells in the retina called Muller cells. Muller cells are vital for the normal function of the retina, and are known to be abnromal late in diabetes. They may also be dysfunctional early in diabetes and could play a significant role in the early chnages seen in diabetes. Therefore a good understanding of how Muller cells change and the time at which they change is vitally important to gain a better undetrstanding of the defects that are associated with diabetes. Furthermore, an understanding of the basic underlying cellular changes that occur in diabetes will aid the development of more specific therapeutic agents in the future.Read moreRead less
Multidimensional Coding Of Visual Information In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$359,431.00
Summary
Although both the retina and visual cortex are part of the central nervous system, the coding of visual information in the two laminar structures differs markedly in that all three dimensions of the cortical sheet are used to code multiple response axes but only one dimension of the retinal sheet. This project examines how visual response properties are mapped through the depth of the retina and this will provide a comparatively simple paradigm of complex information processing in the brain.
The Role Of Purines In Photoreceptor Death During Retinal Degeneration.
Funder
National Health and Medical Research Council
Funding Amount
$458,729.00
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.
Molecular Mechanisms Of Photoreceptor Protection In Rat Models Of Degenerative Retinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$277,480.00
Summary
The photoreceptor cells of the eye (rods and cones) are the cornerstones of vision. Without them the complex and rich sense of vision fades into blindness. In 1 person in 4-5,000 - about 5,000 Australians and 1-2 million people world-wide - these cells degenerate spontaneously. The condition which results is known as retinitis pigmentosa (RP); it causes progesses blindness, most often affecting young adults. Despite recent advances in research, there is still no effective cure. The present work ....The photoreceptor cells of the eye (rods and cones) are the cornerstones of vision. Without them the complex and rich sense of vision fades into blindness. In 1 person in 4-5,000 - about 5,000 Australians and 1-2 million people world-wide - these cells degenerate spontaneously. The condition which results is known as retinitis pigmentosa (RP); it causes progesses blindness, most often affecting young adults. Despite recent advances in research, there is still no effective cure. The present work will explore the environmental factors which determine whether photoreceptors last the lifetime of the individual, or die prematurely. The factors which cause their premature death include genetic mutations but also include environmental factors, including the oxygen status of the retina, the brightness of light experienced and the retina's response to stress. We will investigate the mechanisms by which the retina protects photoreceptors in the face of stress, and how it prepares itself for future insults. Several of these mechanisms have already been identified. The present work will investigate their function at the molecular level, to gain the understanding need to influence their operation. Understanding the response of photoreceptors to these environmental stresses will make it possible to slow the degeneration by manipulating the retinal environment.Read moreRead less
Oxygen Toxicity As A Factor In Retinal Degenerations: Genetic And Environmental Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$269,250.00
Summary
This project will explore the mechanisms underlying a group of blinding diseases called Retinitis Pigmentosa (RP). They are caused by the death or degneration of the light-receptive cells of the retina of the eye (photoreceptors). It is well established that many forms of RP are caused by genetic mutations but many cases (40-50%) occur 'sporadically', i.e. without a family history. Further there is growing evidence that the rate at which genetic forms of the disease progress is strongly influenc ....This project will explore the mechanisms underlying a group of blinding diseases called Retinitis Pigmentosa (RP). They are caused by the death or degneration of the light-receptive cells of the retina of the eye (photoreceptors). It is well established that many forms of RP are caused by genetic mutations but many cases (40-50%) occur 'sporadically', i.e. without a family history. Further there is growing evidence that the rate at which genetic forms of the disease progress is strongly influenced by environmental factors, particularly light and oxygen. To analyse how these environmental factors affect the stability of the retina, we will use a range of techniques (including gene array technology) to study the molecular events which link light or oxygen stress to photoreceptor death. The work will be done in mouse 'models' of the disease. It is increasingly well established that the rodent (rat and mouse) retina and human retina share a basic structure and functional detail. These models allow intensive investigation, with results which are directly applicable to human disease. Our principal emphasis will be on three aspects of these models: (1) the molecular mechanisms induced in the retina by light stress or oxygen stress; (2) the role of mitochondria (cellular organelles essential for both cell metabolism and cell stability; and (3) genes which regulate the vulnerability of photoreceptors to oxygen stress. RP has been recognised for nearly 100 years as a leading cause of blindness in young adults. It is usually diagnosed in the young adult as a failure of night vision, but the prognosis is grim (relentlessly progressive loss of vision), and there is still no effective treatment. The work proposed will contribute to our understanding of the basic mechanisms involved, and will explore some approaches to therapy for, or at least to mitigation of the blindness of RP.Read moreRead less