The retina lines the back of the eye and sends multiple movies of the visual world to the brain. This project aims to investigate how these multiple information channels are created. Descriptions of the basic pattern of wiring in the healthy retina will help clinical researchers to understand the disruptions that occur in visual disease. The precision of normal retinal wiring also delineates the precision required to restore normal function to a diseased or degenerating eye.
The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells w ....The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells which line the back of the eye). It is characterised by a very high density of cone photoreceptors, and is essential for high-acuity vision. This makes the fovea the most important part of the primate retina, but the high density of nerve cells there is thought to be the reason why the fovea is especially vulnerable to disease and age-related degeneration. Our aim is to analyse, using high-resolution microscopic techniques, the connections of koniocellular-pathway cells within the retina. We specifically aim to discover whether the koniocellular pathway contributes to foveal vision. Recent work from our and other laboratories has shown that many koniocellular-pathway cells receive functional connections from short-wavelength sensitive (blue) cone photoreceptors. Thus, our study will provide new insights into the connectivity of blue-cone pathways in the fovea. Although these experiments address basic scientific questions, they can lead to improved clinical practice. Understanding the wiring diagram of the retina can inform clinical studies of conditions such as glaucoma, and helps to give a rational basis for development of treatments. For example, dysfunction in blue-cone pathways is an early sign of glaucoma, so understanding the connections of blue-cone pathways in the fovea can lead to improved methods for early detection of this leading cause of blindness.Read moreRead less
The Cellular Organisation Of Interneurones In Human Retina
Funder
National Health and Medical Research Council
Funding Amount
$526,454.00
Summary
Our goal is to determine the numbers and types of nerve cells in the human retina: the part of the eye where visual processing starts. This data will serve as a baseline against which effects of visual disease can be measured.
The Role Of Gliosis In Advanced Retinal Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$457,785.00
Summary
The development of treatments that restore vision assumes that the output neurons of the retina remain intact. Yet, there is now considerable evidence that the neurons that signal from the retina to the brain are altered in those that have degenerative diseases of the retina. Here, we will examine the cause of these cellular changes in an animal model and seek to prevent the loss of output neurons. This information is crucial for the development of treatments that seeks to restore vision.
Understanding the structure of the human retina is important for understanding normal visual function. The goal of this study is to supply data on the distribution, density and connectivity of nerve cells in the human retina. Our study will provide a foundation for areas of clinical investigation of the human retina.
We will investigate changes in the retina secondary to disease process and try and modify them to allow a longer time frame for intervention. These changes (remodelling) are detrimental to visual function and the effectiveness of measures aimed at restoring vision, eg, bionic eye.
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
Targeting GDNF Family Ligand (GFL) Signalling To Treat Inflammatory Bone Pain
Funder
National Health and Medical Research Council
Funding Amount
$329,285.00
Summary
Pain associated with bone marrow oedema syndromes, osteomyelitis, osteoarthritis, fractures and bone cancer causes a major burden on individuals and health care systems in Australia and worldwide. In this application, we will explore specific signalling pathways that we have identified in nerves that code bone pain. This will provide an opportunity for the rational design of highly specific drugs capable of interacting exclusively with molecules that drive pain in these conditions.
Role Of Dendritic Information Processing In Visual Circuit Computations
Funder
National Health and Medical Research Council
Funding Amount
$895,244.00
Summary
Vision is the primary sensory modality in man, and its disturbance carries an enormous socio-economic burden. The dynamic operations of the neuronal assemblies that underlie vision are poorly understood, partly because of an incomplete description of the computational properties of visual neuronal circuits. The aims of the application are to mechanistically dissect defined computational operations of visual neural circuits using advanced electrophysiological and optical recording techniques.