Glaucoma is a progressive, poorly understood blinding disease with limited treatment options. It is characterised by the death of the nerve cells in the eye whose fibres form the optic nerve. Results obtained in the current proposal will lead to a better understanding of key features of the early stages of the disease and, additionally, will explore the potential of a novel therapeutic approach based on regeneration of damaged nerve fibres within the optic nerve.
Intrinsic Hearing Protection Mechanisms: A Pathway To Prevention Of Noise-induced Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$625,900.00
Summary
Noise-induced hearing loss (NIHL) is a significant contributor to the total burden of disease. We recently determined that when the ear is exposed to sustained noise, the cochlea is protected from damage by activation of a specific (P2X2) receptor, evident as reversible hearing adaptation. This study will determine the downstream signalling from this receptor. This will support assessment of vulnerability to NIHL and contribute to development of hearing therapeutics.
Transcriptional Regulation Of Nociceptor Function And Extreme Genetic Pain Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,007,462.00
Summary
Disorders involving untreatable pain have a devastating impact on a patient’s quality of life. To better treat these conditions, we require a basic understanding of how sensory neurons work. In this study we will define the genetic network involved in regulating pain-sensing neurons. We will then search the genome of pain patients looking for coding mutations within this pain transcriptional network, and we will prove these mutations are causative in fly and mouse systems.
Does The Complement System Contribute To Neuropathic Pain?
Funder
National Health and Medical Research Council
Funding Amount
$262,958.00
Summary
Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes ....Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes to neuropathic pain. We have evidence that inflammatory responses play a key role in initiating neuropathic pain. Other evidence suggests that the immune system contributes to neurological diseases and accompanying pain (e.g. Guillain-Barr syndrome and multiple sclerosis). We plan to test the idea that a component of the immune system known as the complement pathway contributes to the development of neuropathic pain following peripheral nerve injury. The outcome of this work will be a better understanding of the way in which nerve injury leads to chronic disorders of pain, including increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
Training-induced Restoration Of Topographic Maps And Vision During Opticnerve Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$379,725.00
Summary
The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, h ....The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, however, over the last decade is the recognition that the adult CNS, particularly after damage, does have a capacity for repair and that appropriate neural activity, produced either via relevant experience or specific training, is essential in driving the repair process to produce useful behavioural recovery. One of the clearest examples comes from our laboratory in which we have recently shown that training animals on specific visual tasks during optic nerve regeneration allows useful vision to be restored; untrained animals are blind via the experimental eye. The advantage of the visual system is that it is a relatively simple part of the CNS with one major class of nerve cell projecting to well defined and accessible brain regions. The significance of the project is that, for the first time, we are able pinpoint specific training-induced effects within identified nerve cells and their connections, a task that is much harder within other CNS regions. In particular, we will examine molecular, anatomical and functional changes that are induced via training and explore whether intervention with blockers of inhibitory neurotransmission further improves the beneficial effects of training. Understanding the changes in nerve cells that underlie the positive effects of training after neurotrauma will have implications for the continuing development of rehabilitation strategies for improved recovery after CNS injury.Read moreRead less