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.
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
A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second grou ....A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second group of plastic phenomena depend upon minute changes in the connections between neurons and these are invoked in the first few days following an injury (synaptic plasticity; changes in the pattern and strength of the connections between neurons). Aside from being model systems, there are also parallels of this plasticity with clinical situations such as losses in hearing and sight, and of the adaptations made by the brain in response to prosthetics (e.g. bionic ear) and resorative surgery but the degree of relevance for these situations is unclear. An intriguing aspect of the experiments on auditory and visual systems is that neurons with inputs from both ears, or both eyes, undergo the plastic changes when the relevant sense organ on only one side is damaged but the other is intact. In fact, on the basis of the limited available evidence, it appears that the changes are independent of there being a normal input from the other side. This is difficult to explain in terms of the modern understanding neuronal plasticity at a cellular level. It is thus proposed to study both auditory and visual models of this brain plasticity with stimuli which are systematically varied to extract the extent of bilateral interaction in the induced plasticity. This will enable prediction of how these plasticity mechanisms will be involved in adaptations made to prosthetics and surgical corrections.Read moreRead less
Structure And Function Of The Third Geniculocortical Pathway In Primates.
Funder
National Health and Medical Research Council
Funding Amount
$296,777.00
Summary
Our understanding of the human visual system has been based on the idea that there are two main nerve pathways from the eye to the brain. One, called the parvocellular pathway, is for colour and detail vision, and the other, called the magnocellular pathway, is for movement perception. Damage to either pathway by disease such as glaucoma, or a lesion such as stroke, will cause specific changes in visual perception and these changes can be used to diagnose the nature of the disease or lesion. We ....Our understanding of the human visual system has been based on the idea that there are two main nerve pathways from the eye to the brain. One, called the parvocellular pathway, is for colour and detail vision, and the other, called the magnocellular pathway, is for movement perception. Damage to either pathway by disease such as glaucoma, or a lesion such as stroke, will cause specific changes in visual perception and these changes can be used to diagnose the nature of the disease or lesion. We will study a recently recognised third subdivision of the visual pathway, called the koniocellular pathway. The properties of koniocellular cells have not previously been studied in anthropoid primates, and their importance for human vision is not well understood. We will study the way that koniocellular cells respond to moving and patterned stimuli, and their connections with the cerebral cortex, in order to determine whether this pathway could contribute to aspects of normal and abnormal visual perception. We will follow up our preliminary evidence that koniocellular cells respond to visual stimuli of the type used to diagnose the early stages of eye diseases such as glaucoma. The results will give us a better understanding of the way that the nervous system processes visual information, and will clarify the basis of disturbances to normal visual function.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.
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
Distribution Of Neurotransmitter Receptors On Identified Cell Populations In The Primate Retina
Funder
National Health and Medical Research Council
Funding Amount
$421,812.00
Summary
Neurons (nerve cells) communicate with each other by releasing chemicals called neurotransmitters at specialized sites called synapses. Each neuron has synaptic receptors, which determine how it will respond to neurotransmitters released by other neurons. The molecular structure and function of these receptors is well understood. Much less is known about the rules that govern which receptor types are expressed by each type of neuron, and how these receptors are distributed to the appropriate syn ....Neurons (nerve cells) communicate with each other by releasing chemicals called neurotransmitters at specialized sites called synapses. Each neuron has synaptic receptors, which determine how it will respond to neurotransmitters released by other neurons. The molecular structure and function of these receptors is well understood. Much less is known about the rules that govern which receptor types are expressed by each type of neuron, and how these receptors are distributed to the appropriate synapses so as to allow the normal function of the nervous system. We will study the distribution of neurotransmitter receptors on identified neurons in the retina. The retina is part of the central nervous system and its highly ordered structure makes it an ideal model nervous system. We will compare the distribution of receptors on neurons that play distinct functional roles in colour and movement detection. These experiments will advance our understanding of the normal functioning of the nervous system.Read moreRead less
Origin And Specificity Of Neuronal Signals For Colour Vision In Primates.
Funder
National Health and Medical Research Council
Funding Amount
$490,500.00
Summary
How do we see colours? What do colour blind people see? Although colour is one of the most important attributes of objects in the visual world, the way that colour is processed in the brain is poorly understood. The aim of this project is to study the way that nerve cells in the eye (the retina) and the visual part of the brain are specialised to transmit signals for colour perception. The visual system of humans and other primates includes nerve cells which are selective for a limited range of ....How do we see colours? What do colour blind people see? Although colour is one of the most important attributes of objects in the visual world, the way that colour is processed in the brain is poorly understood. The aim of this project is to study the way that nerve cells in the eye (the retina) and the visual part of the brain are specialised to transmit signals for colour perception. The visual system of humans and other primates includes nerve cells which are selective for a limited range of wavelengths reflected by objects in the visual world. We will study how this selectivity is generated, by examining how the colour receptors are connected within the retina to the cells which transmit nerve impulses to the brain. Between 5 and 7 percent of male humans have colour vision defects. Many objects which appear clearly different to colour-normal observers cannot be discriminated by colour-defective observers, and entry to professions such as the police and airline industry is restricted for individuals with colour vision defects. We will study the basis of reduced colour perception ability in red-green colour blindness. This will be done by measuring the responses of nerve cells in a species of primate (marmoset) in which many animals have colour vision receptors resembling those of humans with colour vision defects. We will measure the reliability with which individual neurones can transmit signals for colour vision when they receive input from such abnormal receptors. It is known that nerve cells transmit their message within the brain by means of brief electrical impulses called action potentials. In addition to studying the basis of human colour discrimination, the project also addresses one of the fundamental questions of sensory processing, by studying the reliability of the coded message carried by action potentials within the central nervous system.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
Synaptic Connectivity Of Colour Pathways In Primate Retina
Funder
National Health and Medical Research Council
Funding Amount
$367,500.00
Summary
The first step in the visual process occurs when light enters the eye and activates specialised nerve cells called photoreceptors. The photoreceptors for daytime vision (called cones for their cone-like shape) comprise three types, which are sensitive to the long- (red), medium- (green) or short-wavelength (blue) regions of the visible spectrum. Although the properties of the cones are well known, the way in which they are functionally connected to nerve pathways for vision is not clearly unders ....The first step in the visual process occurs when light enters the eye and activates specialised nerve cells called photoreceptors. The photoreceptors for daytime vision (called cones for their cone-like shape) comprise three types, which are sensitive to the long- (red), medium- (green) or short-wavelength (blue) regions of the visible spectrum. Although the properties of the cones are well known, the way in which they are functionally connected to nerve pathways for vision is not clearly understood. Clinical research has shown that reduced sensitivity to blue light is a feature of the early stages of certain visual diseases (for example, glaucoma), so it is important to know how the short-wavelength (blue) cones contribute to visual functions such as form, motion and colour perception. Such knowledge can help to design better tests for diagnosis of visual disorders, and will improve our understanding of the normal function of the visual system in the human brain. In this project the connections of neurones in the primate retina (the nerve cells which line the back of the eye) will be analysed. The blue cones and other nerve cells will be identified using contemporary anatomical methods (double- and triple-label immunocytochemistry) combined with a new method for high-resolution light microscopy, called deconvolution microscopy. Immunocytochemistry is a method borrowed from the field of immunology, where specific antibodies are raised which bind selectively to label specific populations of neurones. Deconvolution microscopy allows rapid and simultaneous visualisation of multiple labelled cell classes, at a resolution close to the limit of the light microscope. Together, these techniques allow the wiring diagram of the blue cones within the retina to be analysed to a higher level of accuracy than previously achieved. The results will improve our understanding of the role of blue-cone circuits in normal vision and visual disorders.Read moreRead less