Research Supervisor Connect
Utilising several different mouse models of corneal nerve injury and dysfunction, neovascularisation, as well as ocular inflammation, our laboratory is focused on discovering novel solutions to the unmet needs in ophthalmology. Accordingly, there is scope for a PhD or Masters HDR student to join the laboratory to explore Thrombospondin-1 through mouse models and in vivo blockade of specific pathways, whole tissue imaging, and RNA and protein expression assays. This work has the potential to lead to development of multiple therapeutics for the treatment of ophthalmic diseases.
A/Prof Chameen Samarawickrama.
Westmead - Childrens Medical Research Institute
Background: The cornea is the clear avascular layer at the very front of the eye that acts as a window to the foreign world. The tight physical barrier on the corneal epithelium, high degree of innervation, and various other factors that mediate corneal immune privilege grant the cornea protection from opportunistic invasion of pathogens and immunologic damage. Distinct populations of resident leukocytes, including antigen presenting cells such as dendritic cells and macrophages, reside throughout the cornea and act as the first line of defence for the host allowing the rapid mobilisation against infiltrating particles. It is hypothesized that the epithelial barrier, local immune populations, relatively high level of innervation and complete avascularity through suppression of angiogenesis and lymphangiogenesis are tightly regulated and interconnected in the ocular surface. Further, ocular surface damage and/or disease will inevitably involve and affect all the interconnected ocular surface components mentioned.
Despite corneal transplantation being the most common tissue allotransplant worldwide, graft rejection remains one of the leading causes of graft failure. Whilst newer surgical techniques have improved patient outcomes, the rate of rejection has remained fairly similar over time. Corneal allografts into first-time non-inflamed and avascular graft beds have approximately a 90% acceptance rate. Although low-risk grafts enjoy a high rate of success, the current mainstay of treatment, topical steroids, has side effects including increased risk of opportunistic infections, glaucoma and cataract formation, and provide limited aid in cases where corneal transplants are grafted into vascularized neurotrophic corneas where the rejection rate in the first two years are as high as 70%. As such, finding an effective treatment that improves the ocular surface milieu has the potential to positively impact the clinical outcomes in these high-risk transplants.
Thrombospondin (TSP)-1 is constitutively expressed in the cornea and plays a significant role in maintaining the cornea’s angiogenic privilege. TSP-1 KO studies have revealed altered corneal innervation, altered lacrimal gland structure and function, as well as mononuclear infiltrates into the lacrimal gland.
This project is an in-depth investigation of the role of TSP-1 in ocular surface leukocyte kinetics, dry eye, and corneal allograft survival.
Research approach equipment: Our group utilises cell cultures and animal models to investigate the role of immune cells, innervation and vascularisation in ocular surface homeostasis and disease states with the goal to assess ocular surface treatments in ameliorating conditions and diseases that can lead to blindness
Key techniques employed: Transgenic mice; in vivo blockade of specific pathways; whole tissue staining; confocal fluorescence Imaging; and RNA and protein expression assays
Impact: We believe TSP1 has the potential to be a potent therapeutic in the management of multiple ophthalmic and corneal diseases including corneal neovascularization and warrants further study.
Research Team: The Translational Ophthalmic Research and Immunology Consortium (TORIC) is based at the Westmead Institute for Medical Research (WIMR). It brings together both the clinical and basic science aspects of medical research to explore and discover novel solutions to unmet needs in ophthalmology.
The opportunity ID for this research opportunity is 2994