Cell Death In The Retina: Analysing The Switch That Triggers Dependency On Target-derived Trophic Factors
Funder
National Health and Medical Research Council
Funding Amount
$428,414.00
Summary
Construction of the developing nervous system in the embryo involves the creation of nerve cells and their connections, but also involves loss of a proportion of these cells prior to maturation. We will study this process of cell death and how developing nerve cells switch on their dependency to survival factors. In so doing we will better understand what happens when brain development goes wrong and also devise new ways to protect nerve cells in the injured or degenerate adult nervous system.
What Is The Effect Of Alzheimer’s Disease On Eye And Can Ocular Changes Be Used As Biomarker For Alzheimer’s Disease?
Funder
National Health and Medical Research Council
Funding Amount
$718,002.00
Summary
Visual symptoms are frequent early complaints in Alzheimer’s (AD) patients. Examining eyes can be a simple, specific and inexpensive way to assess and diagnose AD and fill in an urgent need for a viable biomarker. Retina is unique part of central nervous system that can be imaged non-invasively and thus serves as a ‘window to the brain”. Monitoring the eyes will also help prevent negative effects of AD on vision by way of timely intervention, in addition to providing mechanistic insights in AD.
Is The Eye A Window To The Brain In Sanfilippo Syndrome?
Funder
National Health and Medical Research Council
Funding Amount
$852,967.00
Summary
Study of the retina and optic nerve permits evaluation of central nervous system – these structures contain both neurons and glia and are outgrowths of the developing brain. Therefore, eye examination may allow us to study the brain and monitor brain disease and the effect of therapy. This project will determine whether brain disease in a childhood-onset disorder (Sanfilippo syndrome) and treatment of it, can be monitored in this way.
Assessing The Efficacy Of Safe And Simple Neuroprotective Treatments For Chronic Degenerative Conditions Of The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Current treatments for age-related diseases of the central nervous system (CNS) are limited. We have shown in animal models of acute CNS degenerations that treatment with saffron or low energy infrared light is strongly protective. This project will determine if these treatments prevent CNS damage and dysfunction in animal models of chronic degenerations and add to knowledge of how these treatments work. This research should lay the foundation for testing these novel treatments in humans.
Central Nervous System Dendritic Cells – Guilty Or Not Guilty?
Funder
National Health and Medical Research Council
Funding Amount
$481,594.00
Summary
The central nervous system although structurally and functionally unique, must be able to mount protective immunological responses. However, breakdown in local and central immunoregulatory processes can lead to clinically disabling inflammatory conditions such as uveitis and multiple sclerosis. This project will investigate the role of Dendritic cells in models of autoimmune diseases affecting the eye and brain. The data will greatly aid our ability to design new immunotherapies to treat these b ....The central nervous system although structurally and functionally unique, must be able to mount protective immunological responses. However, breakdown in local and central immunoregulatory processes can lead to clinically disabling inflammatory conditions such as uveitis and multiple sclerosis. This project will investigate the role of Dendritic cells in models of autoimmune diseases affecting the eye and brain. The data will greatly aid our ability to design new immunotherapies to treat these blinding and crippling diseases.Read moreRead less
Retinal Microvascular Signs In Acute Stroke: Prognostic Significance And Relevance To Underlying Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$375,425.00
Summary
This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that asses ....This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that assess size of the small retinal arteries compared to veins (the arteriole-to-venule ratio) and will document other abnormalities, such as microaneurysms, haemorrhages, tortuosity and focal and generalised vessel narrowing and wall opacity. In normal populations these signs are associated with hypertension, inflammation and endothelial dysfunction and predict future stroke. These signs, and their significance have not been systematically studied in acute stroke. This may offer a window into the brain for important subgroups of stroke such as lacunar stroke. It is increasingly hard (and remains technically very difficult) to study the cause of lacunar stroke, affecting 10,000 Australians each year, as lacunar stroke has a lower fatality rate (and thus few opportunities for post mortem studies) but a high disability rate. Lacunar stroke is known to be due to small vessel disease but the exact nature of this disease is unknown. Echocardiography (to identify heart and major blood vessel abnormalities) and carotid duplex scanning (to identify critical stenosis of the major blood supply to the brain) are commonly normal in this type of stroke, and brain scanning with computerised tomography (CT) or magnetic resonance (MR) merely shows the outcome of the small vessel disease. The eye develops as part of the brain and thus retinal vascular abnormalities could add important knowledge to our understanding of stroke and add clinically useful data in the assessment of patients with stroke.Read moreRead less
The Role Of Netrin-DCC In The Development Of The Corpus Callosum
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with ove ....During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with over 50 different human congenital syndromes. Thus understanding how the genes and molecules involved in the formation of the corpus callosum function in normal development can provide the basis for our understanding of what goes wrong in ACC. In this proposal we will investigate the role of the axon guidance molecule Netrin1, and its receptor DCC, in development of the corpus callosum in both a mouse model and in humans with malformations of the corpus callosum. Although Netrin1-DCC signalling has traditionally been associated with mechanisms of axon guidance, we hypothesize that these molecules may play a different role, specifically in cellular adhesion and ultimately in the fusion of the two cerebral hemispheres, in a manner that allows the corpus callosum to form. A second role for Netrin1-DCC signalling may be in the guidance of these axons once the midline has fused correctly and we investigate this in Aim 2 of the proposal. Finally, we are collaborating with a paediatric neurologist at UCSF, who has identified several mutations in the DCC gene in patients with ACC. In Aim 3 we test whether these mutations disrupt the function of DCC in callosal axon pathfinding. Understanding how these genes function during development of the brain and how their function may be altered in ACC is crucial to providing a proper diagnosis and prognosis for these patients. Ultimately, understanding more about how these genes function could also lead to prevention of these disorders.Read moreRead less
Blood-brain Barrier And White Matter Damage In The Immature Rat Brain Following Systemic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$353,173.00
Summary
Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infecti ....Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infection and brain damage, one form of which is cerebral palsy, is well established from clinical epidemiological studies, but the biological mechanism of this link is unknown. The CIs' group has recently shown that the condition can be reproduced in neonatal rats at a stage of brain development in the rat that is equivalent to the critical time in human brain development when infection may be associated with brain damage. The CIs' group has shown that an induced inflammatory state similar to a bacterial infection, results in damage to blood vessels in the white matter and is associated with changes in white matter, as occurs in affected babies. The purpose of this study is to understand the nature of the damage to white matter blood vessels and the mechanisms by which materials in blood, which in the normal brain do not pass from the blood to the brain across the blood-brain barrier, are able to do so via the inflammation damaged blood vessels. The study also aims to show whether it is components of the blood entering the brain via the damaged blood vessels that are responsible for the damage to white matter in the immature brain. The outcome should lead to development of ways to improve clinical care of women who acquire infections during pregnancy.Read moreRead less
Targeting Central Inflammation To Combat Obesity And Obesity-related Cognitive Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
The current obesity epidemic means many of us will suffer from overweight or obesity for at least some of our lives. My findings show obesity can cause inflammation throughout the brain including in regions related to learning and memory. Here I hypothesize that obesity induces long-term changes in the brain’s immune cells, that this can explain why we see susceptibility to cognitive decline in obese individuals, and that we can reverse these negative effects by targeting these immune cells.