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
Engineered Antibody Fragments For The Diagnosis And Treatment Of Eye Disease
Funder
National Health and Medical Research Council
Funding Amount
$196,886.00
Summary
We plan to investigate the use of genetically-engineered antibody fragments in the diagnosis and treatment of clinically-important human eye diseases. The work will be carried out in experimental models, but the goal is to develop a new class of drugs that will be widely applicable in human inflammatory eye disease and eye infections. Antibodies are natural proteins, found in blood and body secretions, that protect humans from infections. However, they can be made in the laboratory and monoclona ....We plan to investigate the use of genetically-engineered antibody fragments in the diagnosis and treatment of clinically-important human eye diseases. The work will be carried out in experimental models, but the goal is to develop a new class of drugs that will be widely applicable in human inflammatory eye disease and eye infections. Antibodies are natural proteins, found in blood and body secretions, that protect humans from infections. However, they can be made in the laboratory and monoclonal antibodies in particular - those with a single defined specificity - have found widespread use in many medical applications. For the past 15 years, monoclonal antibodies have been used therapeutically, that is, they have been administered to humans to treat some diseases. Antibodies are big proteins that have multiple functions. Their very size and the multiplicity of their actions prevent their use in some therapeutic situations. In recent years, advances in genetic engineering and biotechnology have developed to the extent that small fragments of monoclonal antibodies can be produced in the laboratory with relative ease. Such fragments should have very substantial advantages over intact antibodies in the diagnosis and treatment of human eye disease. Engineered antibody fragments hold enormous potential for ophthalmic use, especially if they can be administered topically as eye-drops. In this project, we aim to determine whether antibody fragments can be used in the diagnosis and the treatment of four potentially blinding conditions: acute anterior uveitis and corneal graft rejection, which are inflammatory eye diseases, and herpetic keratitis and Acanthamoeba keratitis, which are eye infections.Read moreRead less