The Role Of Dopamine And Other Neuromodulators As Light Signals In The Inner Retina: A Link To Night Blindness Disorders
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-ligh ....Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-light switch can have fatal consequences. Night blindness is a symptom characterised by reduced vision in the dark and slow adaptation to dim light. Some congenital night blindness disorders are caused by mutations in the photoreceptor calcium channels which mediate signal transmission. Additionally, patients treated with neuroleptics, a group of drugs which affect the dopaminergic system, suffer night vision disorders. Dopamine acts as a light signal in the retina. AII amacrine cells are pivotal neurones for night vision segregating two channels (ON and OFF) which convey visual information. AII cells are modulated by dopamine and thus, represent interesting targets to study the role of dopamine in the dark-light switch. Much is know about the action of dopamine on transmission of ON signals channelled by AII cells. However, its action on the OFF channel is largely unknown. We believe that some night vision disorders originate by imbalance in the dopaminergic system in the retina and its effects on AII cells. We will test our hypothesis by studying the modulatory effect of dopamine on calcium dependent signal transmission between AII cells and their partners in the OFF channel. Our hypothesis will be further tested by using animal models in which dopamine receptor function is altered. The results of these studies will provide us with an invaluable model to understand the physiological basis of the dark-light switch and of the role of dopamine in night vision disorders.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
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.
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.
Novel Retinal Architectural Vascular Signs And Risk Of Cardiovascular Disease: The AusDiab Study
Funder
National Health and Medical Research Council
Funding Amount
$754,254.00
Summary
Cardiovascular disease (CVD) and diabetes are major health problems. Identifying 'people at risk' is critical to design preventative strategies. We have developed new computer software to measure detailed characteristics of retinal vessels. By appling this system to predict CVD or diabetes in the AusDiab Study we aim to find 'the best combination of risk factors' to predict CVD and diabetes. This will open up the possibility of new risk assessment using a simple 'eye scan.'
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
Genetic Associations Of Early Retinal Pathologic Phenotypes: Data Pooling And Meta-analyses Of Multiple Populations
Funder
National Health and Medical Research Council
Funding Amount
$736,481.00
Summary
We aim to use data already collected from multiple population-based studies to investigate the likely pathogeneses of early retinal phenotypes that are either markers for cardiovascular risk or precursors of a blinding condition. Understanding if there are genetic susceptibilities for these phenotypes, and if so, how they together with environmental exposures jointly influence the occurrence of the diseases may be key to reduce the burden from cardiovascular disease and blindness.
Properties Of Human Photoreceptors Measured Using A Scanning Laser Ophthalmoscope To Illuminate And Image The Retina
Funder
National Health and Medical Research Council
Funding Amount
$352,000.00
Summary
Vision begins with the detection of light by the rod and cone photoreceptors in the retina lining the interior of the eye. Although much is already known about the way that light is detected and the signals are processed, a great deal remains to be learned. Some of the outstanding questions could be answered using modifications to a relatively new instrument called a scanning laser ophthalmoscope (SLO) which provides images of the interior of the eye. The aims of this project are to develop a mo ....Vision begins with the detection of light by the rod and cone photoreceptors in the retina lining the interior of the eye. Although much is already known about the way that light is detected and the signals are processed, a great deal remains to be learned. Some of the outstanding questions could be answered using modifications to a relatively new instrument called a scanning laser ophthalmoscope (SLO) which provides images of the interior of the eye. The aims of this project are to develop a modified SLO, which is able to measure the levels of visual pigment (rhodopsin) in the living eye, which is also able to deliver visual stimuli to the eye, and which finally is extended to use adaptive optics so that it can image and excite individual cone photoreceptors. Using this device, we will be able to measure the regeneration of visual pigment following exposures to intense illumination, to help explain the slow recovery of visual sensitivity after intense light. We will also be able to measure the electroretinogram (ERG) from localized retinal areas, to investigate how the properties of the photoreceptor cells vary across the retina. And finally we will be able not only to visualize the individual tiny cone photoreceptors, but also to stimulate them selectively, so that we can determine the responses of the different classes of cone (red-, green-, and blue-sensitive cones) in the living human eye.Read moreRead less
The Functional Basis Of Direction Selectivity In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
Motion is an everday visual experience, and in this project we are attempting to explain how our brains are able to detect the direction in which an object is moving. Surprisingly this is first accomplished within the retina, the light-sensitive system of neurons at the back of the eye. Thus the eyes are able to tell the brain in which direction an object is moving. So the question becomes, how do the eyes do it? We know that there is a special class of neurons, the direction-selective ganglion ....Motion is an everday visual experience, and in this project we are attempting to explain how our brains are able to detect the direction in which an object is moving. Surprisingly this is first accomplished within the retina, the light-sensitive system of neurons at the back of the eye. Thus the eyes are able to tell the brain in which direction an object is moving. So the question becomes, how do the eyes do it? We know that there is a special class of neurons, the direction-selective ganglion cells, which are able to detect the direction of image motion. The activity of these cells is increased by excitatory connections and reduced by so-called inhibitory connections. This project aims to identify the neural origin of the inhibitory connections, and discover how the excitation and inhibition work together to compute the direction of motion.Read moreRead less