Despite the acknowledged limitations of ophthalmic medication by means of topical guttae therapy, including toxicity, inefficiency and poor compliance, there has been no success in developing a true alternative suitable for a wide range of conditions. The availability of a simple, safe efficacious means of prolonged topical ophthalmic drug delivery would alter the practice of ophthalmology worldwide, with reduced morbidity, improved compliance and direct and indirect health savings. Poor patient ....Despite the acknowledged limitations of ophthalmic medication by means of topical guttae therapy, including toxicity, inefficiency and poor compliance, there has been no success in developing a true alternative suitable for a wide range of conditions. The availability of a simple, safe efficacious means of prolonged topical ophthalmic drug delivery would alter the practice of ophthalmology worldwide, with reduced morbidity, improved compliance and direct and indirect health savings. Poor patient compliance with topical guttae therapy is increasingly recognised as a source of significant morbidity. The occurrence of such a breakthrough in Australia would result in Australia benefiting from the boost to a medical biomaterial industry based here, with a large export market for a high value-m3 product. During the next phase of research for this project, over 1 year, we aim to do the following: Phase I: Manufacture a range of prototype devices, with variations in sponge and surface composition and evaluate these devices using a Sintech mechanical tester for elasticity and strength and by light and environmental scanning electron microscopy for structure and porosity. The liquid loading capacity will also be measured for each variant. Phase II: Using both hydrophilic and lipophilic models, drug loading and release kinetics will be assessed in vitro in a continuous flow system, with drug concentrations being measured by UV-Vis and HPLC. Drug stability within the devices will also be assessed. Phase III: Having determined the optimum sponge formulation and release kinetics in vitro, a pilot study will be undertaken to assess drug release in an animal model. Loaded devices will be placed within the inferior fornix the rabbits for specified periods from 0.5 to 96 hours, then removed so that drug levels remaining in the device can be assessed. After a 2 week flushing period, the experiments will be repeated but with animals being sacrificed at the end of the wearing period so that device levels in intraocular tissues and fluids, as well as remaining in the devices, can be determined at these times, with appropriate controls (‘blank’ devices and guttae therapy). This study will also fulfil the requirements for new device tolerance testing as specified by Regulatory authorities, as animals will be monitored for signs of irritation and histological studies will allow any evidence of inflammation to be identified. These studies do not allow evaluation of the device in a model diseased eye, nor attempt to establish drug loading levels required for human subjects, as there are differences in drug transport across the ocular surfaces of rabbits and humans, but will allow sufficient proof-of-principle for further development to occur.Read moreRead less
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