Do Activated Retinal Microglia Mediate Neurotoxicity In Background Diabetic Retinopathy?
Funder
National Health and Medical Research Council
Funding Amount
$435,589.00
Summary
Diabetic retinopathy, a frequent complication of Type 1 and Type 2 diabetes, is the commonest cause of blindness in working age individuals. Prior to the growth of blindness-causing new vessels in the eye we now know that there is a gradual loss of neurons in the retina. This project will investigate whether the resident immune cells in the retina, which are normally neuroprotective, become neurotoxic during episodes of systemic inflammation (e.g. bacterial or viral infections).
The Role Of Gas6 And The TAM Receptors In Central Demyelination
Funder
National Health and Medical Research Council
Funding Amount
$506,416.00
Summary
In Multiple Sclerosis, oligodendrocytes, the myelin-producing cells of the brain, are damaged and myelin is lost in a process called demyelination. This process also involves the brain's immune cells, called microglia. Both cell types are influenced by a factor called Gas6, which signals through proteins called Tyro3, Axl and Mer. We have shown that levels of Gas6 can affect the severity of demyelination in mice. We plan to further study the effects of these proteins during demyelination.
Role Of Osteopontin In Ischemic-like Injury To The Retina
Funder
National Health and Medical Research Council
Funding Amount
$357,862.00
Summary
The molecule osteopontin (OPN) is implicated in the response of certain tissues to disease. We have new evidence that the level of OPN in the visual retina increases markedly following injury. We hypothesise that OPN is produced by specialised retinal cells in response to injury and functions to promote the survival of nerve cells. The proposed research seeks to investigate this hypothesis and the results will contribute to a greater understanding of the role of OPN in retinal diseases.
TNF Traffic And Secretion In Astrocytes And Microglial Cells: Unveilling New Targets For Ischemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$585,070.00
Summary
Neurodegenerative disorders share a similar pathway to disastrous neurotoxicity, which occurs through the release of cytokines such as tumour necrosis factor-a (TNF) from glial cells. TNF controls inflammation but its excessive secretion in the brain is highly detrimental. The mechanism of TNF secretion is unknown but strategies aimed at reducing it have therapeutic potential. This grant proposes to study TNF discharge to find new ways to reduce secretion and confer protection in a stroke model.
Astrocytes And Mural Cells In The Retina: Normal Development And Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$679,616.00
Summary
The blood vessels that supply the nerve cells of the brain and retina are associated with support cells known as mural cells and astrocytes. Whereas astrocytes both ensure that the vessels do not leak and produce factors that induce vessel growth, mural cells control blood flow and are thought to promote vessel stability. We aim to characterise the development of astrocytes and mural cells as well as the interactions of these cells with blood vessels that influence vessel shape, growth, and loss ....The blood vessels that supply the nerve cells of the brain and retina are associated with support cells known as mural cells and astrocytes. Whereas astrocytes both ensure that the vessels do not leak and produce factors that induce vessel growth, mural cells control blood flow and are thought to promote vessel stability. We aim to characterise the development of astrocytes and mural cells as well as the interactions of these cells with blood vessels that influence vessel shape, growth, and loss. Aging is associated with changes in the vasculature of the central nervous system that confer a predisposition to certain conditions, such as dementia, caused by abnormal blood supply and consequent nerve cell death. We plan to investigate the contribution of astrocytes and mural cells to the vascular changes that accompany aging. These studies may lead to the development of interventions to prevent such changes and their associated pathologies. Finally, astrocyte degeneration is implicated in various neuropathological conditions, including dementia, Alzheimer's disease, and trauma. We aim to purify and characterise a population of astrocyte precursor cells whose transplantation might result in the repopulation of damaged regions of the central nervous system.Read moreRead less
The Translocator Protein (TSPO) As A Novel Target For The Treatment Of Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$629,260.00
Summary
Alzheimer's disease (AD) is the most prevalent dementia, characterized by progressive loss of memory. An estimated 230,000 Australians currently suffer from AD, causing a huge impact on their families and carers, as well as on national finances. The present therapies are very limited, and there is no cure. Thus, there is a need for novel treatment strategies. We have developed novel drugs that represent an innovative approach to the treatment of AD.
Cellular Responses To Oligodendrcyte Apoptosis: Modeling The Early Pathogenesis Of Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$460,037.00
Summary
In Multiple Sclerosis, oligodendrocytes (the myelin-producing cells of the brain) are damaged and myelin is lost. This process results in damage to nerve cells. We have generated a model of oligodendrocyte death that results in nerve cell damage. We will use this model to understand how nerve cells become damaged when oligodendrocytes die and whether the brain can make new oligodendrocytes to protect nerve cells from further damage.