Cyclic Nucleotide Induced Degeneration In The Vertebrate Retina
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Retinitis Pigmentosa is a leading cause of human blindness that is currently untreatable. Elevated cyclic nucleotide levels have been shown to have a causal link with the degenerative process. This proposal will develop animal models of retinal degeneration as well as use a genetic mutant showing elevated cyclic nucleotides to identify the mechanism for retinal degeneration. In addition, potential therapeutic options will be investigated using currently available drugs.
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
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.
Sensory Neuronal Pathways From The Lower Genital Tract Of Females
Funder
National Health and Medical Research Council
Funding Amount
$397,224.00
Summary
Many women experience severe debilitating pain upon normally innocuous contact with their genitalia. The causes of this pain are unknown. Therefore, this project will use a suite of sophisticated microscopic and electrical recording techniques to identify the neural pathways that transmit sensation, including pain, from the female lower genital tract. Our new data will help create a rational basis for understanding and treating the physical basis of genital pain in women.
The Role Of Integrins In The Regulation Of Scleral Remodelling During Pathological Myopia Development
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change and this is a complex process, driven by the scleral cells and involving the synthesis of structural components and activity of enzymes which breakdown scleral structure. The aim of this project is to investigate the role of specific scleral proteins (integrins) in high myopia. Integrins reside on the surface of the scleral cells and communicate information about the changes going on in the surrounding sclera. We predict these proteins are important in keeping the cell informed of the local biochemical and biomechanical changes in the sclera and in driving the cell to rapidly adapt to these changes. The project will provide a greater understanding of the process of scleral thinning in high myopia and allow us to test the potential of integrins as therapeutic targets in the sclera, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.Read moreRead less
Therapeutic Regulation Of Matrix Metabolism To Stabilise The Biomechanical Properties Of The Sclera In High Myopia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change. A complex process, involving the synthesis of structural components and the activity of enzymes that breakdown these structural components, is at work in the sclera of eyes that are rapidly enlarging. The aim of this project is to intervene in the biochemical processes that have already been shown to be involved in excessive eye enlargement. We will use both therapeutic agents and innovative gene therapy techniques to reverse the biochemical changes that occur in the sclera of rapidly enlarging eyes. We predict that these therapies will result in a sclera that is more resistant to being stretched and an eye that has less pathology. The results from this study will provide us with potential therapeutic strategies for the treatment of eyes that are enlarging excessively, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.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