Studies Of Antigen Presenting Cells In The Anterior Segment Of The Eye And Their Role In Immune-mediated Ocular Disease
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
Dendritic cells (DC) are considered the 'sentinels' of the immune system because they are capable of trapping antigenic material derived from invading organisms such as bacteria and viruses in peripheral tissues-organs (skin, gut, respiratory tract etc) and then transporting these antigens to the lymphoid organs where they 'alert' the immune system to potential 'dangers' and elicit appropriate T cell responses. If the antigens are novel this mechanism forms the basis of primary cell-mediated imm ....Dendritic cells (DC) are considered the 'sentinels' of the immune system because they are capable of trapping antigenic material derived from invading organisms such as bacteria and viruses in peripheral tissues-organs (skin, gut, respiratory tract etc) and then transporting these antigens to the lymphoid organs where they 'alert' the immune system to potential 'dangers' and elicit appropriate T cell responses. If the antigens are novel this mechanism forms the basis of primary cell-mediated immune responses. Previously 'educated' T cells may upon contact with antigens in the periphery (when presented by other antigen presenting cells [APCs], such as macrophages) become activated. This forms the basis for secondary immune responses. Immune and inflammatory responses in the eye are held in check to avoid permanent damage to the delicate tissues and maintain visual function. The mechanisms which regulate immunological responses in the eye are only now becoming clear. Studies in the Chief Investigators laboratory over the last 7 years have been aimed at unravelling the life cycle and function of APCs in the eye. The present study has three specific aims: 1) Determining whether DC in the eye once they have taken up antigens migrate to the spleen or local lymph nodes? 2) The second aim of this project is to use an animal model of uveitis and transfer fluorescent labelled donor T cells to study the events in the living eye which lead to autoimmune uveoretinitis. In particular we wish to identify the cells that present antigen to infiltrating lymphocytes. 3) Patients often develop posterior uveitis (an autoimmune condition) after a cold or bacterial infection. We aim to mimic conditions of acute inflammation in the eye to see whether this may secondarily predispose the eye to attack by autoreactive lymphocytes.Read moreRead less
GENETIC AND FUNCTIONAL CHARACTERISATION OF ERAP1 VARIANTS ASSOCIATED WITH ANKYLOSING SPONDYLITIS.
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Ankylosing Spondylitis is a progressive arthritis which affects the back and causes the back joints to fuse. The project seeks to investigate the role of the ERAP1 protein and the gene which is the blueprint for the ERAP1 protein in causing Ankylosing Spondylitis. This will be through resequencing the gene, investigating the action of the different ERAP1 proteins and the effect of ERAP1 deficiency in mice.
First-in-Field Study Of Mechanisms Operating In Post-Ebola Eye Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,985.00
Summary
Ebola virus disease is a life-threatening illness with no treatment. Survivors of the disease are at risk of uveitis - inflammation inside the eye - related to the ability of Ebola virus to persist in the eye. Our research will examine the cellular and molecular events that occur in an eye that harbours Ebola virus. This work will be an important step towards the development of treatments for uveitis caused by Ebola virus.
Parasitic and viral infections involving the retina are serious eye conditions that are poorly understood and lack effective treatments. My PhD studies will focus on how human retinal cells fight infections caused by the Toxoplasma parasite, and dengue and Ebola viruses. The results of my investigations will inform the development of better treatments for these blinding eye diseases.
Regulation Of ICAM-1 Expression In Human Retinal Endothelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$565,967.00
Summary
Posterior uveitis is an inflammation that occurs within the eye and may result in blindness. Present treatments are not directed specifically at the inflamed tissues, and they may be ineffective and cause toxicity. This research aims to identify molecules controlling the entry into the eye from the bloodstream of the white blood cells that cause the disease. The results should suggest new targets for safer drugs to treat patients with posterior uveitis.