Pterygia, one of the most common ocular complaints in Australia and worldwide, are thought to originate from overexposure to UV light. We propose that UV-irradiation stimulate certain cells in the eye to produce cytokines, growth factors and enzymes which degrade scaffold proteins such as collagens. These enzymes may play a key role in the progressive and invasive nature of pterygia. Dissecting the mechanism(s) by which UV light induces these proteins will lead to new and more reliable therapies ....Pterygia, one of the most common ocular complaints in Australia and worldwide, are thought to originate from overexposure to UV light. We propose that UV-irradiation stimulate certain cells in the eye to produce cytokines, growth factors and enzymes which degrade scaffold proteins such as collagens. These enzymes may play a key role in the progressive and invasive nature of pterygia. Dissecting the mechanism(s) by which UV light induces these proteins will lead to new and more reliable therapies for the treatment of pterygia.Read moreRead less
The Roles Of Beta-catenin, APC And The Wnt/beta-catenin Pathway In Lens Development And Cataract
Funder
National Health and Medical Research Council
Funding Amount
$456,764.00
Summary
Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epi ....Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epithelial cells. However, considerably less is known about factors that regulate formation of the epithelium itself. As the epithelial cells are affected in some types of cataract it is vitally important to understand the mechanisms that control formation and maintenance of these cells. Our previous studies have identified a growth factor family (TGF-beta) that causes epithelial cataracts. Importantly, our recent studies have identified another growth factor signalling pathway (Wnt-beta-catenin) as being essential for the formation and maintenance of the lens epithelium. We hypothesise that this pathway is disrupted dring cataract formation. This project uses state of the art tools and techniques to investigate the role of two central molecular components of this Wnt pathway (APC and beta-catenin) in the developing lens. By genetically manipulating the activity of these proteins in the mouse lens we will investigate the roles these molecules and the Wnt signalling pathway play in lens development and whether inappropriate activity results in abnormal development or cataract. We will also be able to investigate whether modulating this pathway affects the formation of epithelial cataracts by TGFbeta. The results will provide detailed information on how these molecules regulate lens structure and function and have the potential to identify targets for preventing or ameliorating cataracts.Read moreRead less
The GABAergic System In Eye Growth Control And Myopia
Funder
National Health and Medical Research Council
Funding Amount
$318,142.00
Summary
Shortsightedness (myopia) is the most common visual disorder. High myopia is associated with an increased risk of eye diseases. Current treatments do not stop myopia developing or decrease the associated risk of eye disease. The continued worsening of myopia is very concerning. A safe effective treatment that can either prevent myopia or stop its progression to extreme levels is needed. We have data showing that GABA ergic drugs modify myopia. This proposal will determine the mechanisms.
Inductive Interactions Between Lens And Optic Cup Specify Cell Fates
Funder
National Health and Medical Research Council
Funding Amount
$265,500.00
Summary
Normal eye development depends on interactions between embryonic eye tissues. In the front part of the eye inductive interactions between lens and optic vesicle are important for the formation and growth of lens, ciliary body and iris. Our recent studies indicate that a family of developmentally important growth factors, the Wnts, plays key roles in this process. Our proposed studies will examine, for the first time, the role of Wnts in lens, ciliary body and iris development. Specific experimen ....Normal eye development depends on interactions between embryonic eye tissues. In the front part of the eye inductive interactions between lens and optic vesicle are important for the formation and growth of lens, ciliary body and iris. Our recent studies indicate that a family of developmentally important growth factors, the Wnts, plays key roles in this process. Our proposed studies will examine, for the first time, the role of Wnts in lens, ciliary body and iris development. Specific experimental outcomes will show if Wnts are important in promoting the formation and maintenance of the front part of the lens, the lens epithelium. The outcomes will also give us information on the molecules that mediate the effects of Wnts on lens cells and if regulatory factors from the lip of the optic cup-ciliary body can influence the pathways by which Wnts can influence the lens cells. In addition we will learn if lens-derived Wnts have a role in the formation of ciliary body and iris. Identifying factors that regulate the formation of eye tissues is fundamental to understanding the molecular basis of eye disease. For example, cataract is the most common cause of blindness in the world. Cataract surgery is the most common surgical procedure and is placing an ever-increasing burden on health care budgets. Cataracts that most commonly require surgery usually involve abnormal growth and behaviour of lens cells such as occurs in posterior subcapsular cataract and posterior capsular opacification (also known as aftercataract because it occurs subsequently to cataract surgery). Identifying molecules and mechanisms that are involved in normal formation and growth of lens cells is fundamental to understanding these diseases. In addition, as it is well known that the lens is required for the normal formation of the front part of the eye, including the ciliary body and iris, results from this study may also shed light on some developmental abnormalities such as small eye.Read moreRead less
Novel Ophthalmic Topical Formulation Targeting Molecular Pathogenesis Of Corneal Haze
Funder
National Health and Medical Research Council
Funding Amount
$296,090.00
Summary
Presently, no drugs are proven to cure corneal haze/scarring, major leading cause of global blindness. Haze is caused by eye trauma, infections or refractive laser surgeries. We aim to test a non toxic, novel ophthalmic topical formulation developed to act on molecular and cellular targets of haze formation. The successful completion of the study will determine formulation’s optimal dose, safety and efficacy for its future potential clinical use in reversing corneal scarring/haze without side ef ....Presently, no drugs are proven to cure corneal haze/scarring, major leading cause of global blindness. Haze is caused by eye trauma, infections or refractive laser surgeries. We aim to test a non toxic, novel ophthalmic topical formulation developed to act on molecular and cellular targets of haze formation. The successful completion of the study will determine formulation’s optimal dose, safety and efficacy for its future potential clinical use in reversing corneal scarring/haze without side effects.Read moreRead less
THE ROLE OF MONOCYTIC LINEAGE CELLS IN MODELS OF CORNEAL DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Vision relies on sharp, focused undistorted images passing through the cornea, the clear 'window' at the front of the eye. Corneal disease causes over 5 million cases of blindness worldwide. In patients who damage the delicate covering of the cornea, due to trauma or contact lens wear, there is an increased risk of infection that may lead to blindness. This project will study the ways in which immune cells in the cornea detect invasion by potential pathogens.
Anti-vascular Endothelial Growth Factor-B As A Biologic For Treating Eye Disease
Funder
National Health and Medical Research Council
Funding Amount
$464,295.00
Summary
We plan to show that an engineered antibody fragment against vascular endothelial growth factor-B is an effective therapeutic drug for two eye diseases, corneal neovascularization and age-related macular degeneration. The innovative aspects of this approach are that it may be safer, and have a different spectrum of activity, than existing ophthalmic anti-angiogenic agents. Furthermore, it may be effective for corneal disease when administered as an eye-drop.