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Research Centre

Physiology and Pharmacology

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Physiology and Pharmacology

The Physiology and Pharmacology Group is comprised of a multidisciplinary team of researchers studying the underlying physiology of some of the most important eye diseases in our community.

Many of the techniques established are unique to our group, requiring a combination of technical skill and novelty of approach. Based on the results obtained from more than 25 years of basic research there are now several new avenues of clinical therapy that are being investigated.  These include improved techniques for laser treatment of ischemic retinal diseases such as diabetic retinopathy, new surgical approaches to glaucoma surgery, robotic surgery systems, and pharmacological approaches to restoring normal blood flow. This is in addition to our studies of the physiology of the retina in health and disease.

Research Projects

Oxygen is the most vital nutrient required to support retinal function. Using microelectrodes with tip diameters of one thousandth of a millimeter, we are identifying which layers of the retina require the most oxygen.  This then indicated which retinal components are most susceptible to insufficient oxygen supply. Perhaps the most important finding to date has been that there are specific layers within the inner retina that dominate inner retinal oxygen consumption. These layers, the plexiform layers, contain cells that perform much of the signal processing required in the inner retina.  They are also the sites of much of the retinal pathology seen in ischemic diseases such as diabetic retinopathy.  This observation has opened up a new avenue of research aimed at suppressing the oxygen requirements of these cells, thereby making the retina more resistant to the effects of reduced oxygen supply.

A great deal of clinically relevant information is being obtained from studies of human donor eyes. Specially developed perfusion and staining techniques are being used to fix and label key cellular structures in the human eye. Combined with state-of-the-art confocal microscopy techniques we are building a better picture of the vascular and neuronal components of the human eye and how these are affected by ageing and retinal disease. These ongoing studies have the potential to identify new mechanisms responsible for the sight threatening consequences of a range of retinal diseases.

Nutrient supply to the eye and the efficient removal of waste products is achieved by blood flowing through the network of vasculature within the eye.  Retinal ischemia (inadequate blood flow) is a major component in many retinal diseases. We have a number of techniques for measuring ocular blood flow, and we are looking into the effects of different types of retinal disease on the proper regulation of blood flow.  Because the retina needs to be largely transparent, the retinal circulation has evolved to have rather special properties.  Because the retina must be largely transparent ( to allow light to pass through and reach the photoreceptors), the vascular network is relatively sparse. However, the retinal vessels have a powerful ability to locally regulate blood flow in response to changing demands or supply conditions.  This powerful autoregulatory ability appears to be compromised in many disease states.  Understanding the mechanisms responsible for these effects will ultimately tell us how to target therapeutic strategies to overcome the problem or ameliorate its effects.

We have a range of in vitro preparations for studying the anatomy, physiology and pharmacology of different components of the ocular circulation. At the smallest end of the scale we are able to study the vasoactive properties of individual retinal vessels.  Tiny tubes are inserted into either end of the vessel and test solutions are passed through the vessel in much the same way that blood normally flows. This is technically very demanding since the vessels are typically only 100 microns in diameter.  Potentially vasoactive drugs can be added into the perfusing solution and the effects on the diameter of the vessel determined.

Many naturally occurring or induced models of retinal disease can be studied in the laboratory. In this way we can begin to understand the dominant mechanisms responsible for the human diseases such as diabetic retinopathy, retinal degeneration, and ischemic diseases of the retina following blockage of retinal vessels.  Through a process of national and international collaborations we have been using our unique technologies to measure blood flow and oxygen metabolism in the eyes of laboratory rats with diseases of greatest relevance to clinical ophthalmology.

We are investigating new techniques for using laser therapy in the prevention of the sight threatening consequences of diabetic retinopathy and retinal ischemia.  Our approach is to use better targeted therapy and the minimum level of laser treatment required to produce the therapeutic benefit.  This involves research into the interaction between different wavelength lasers and the retinal tissue, as well as the use of energy modulation of the laser to confine the laser therapy to specific cell types.

New methods of surgical cutting are being investigated. The combination of highly localized laser energy and the robotically controlled manipulation of the cutting instruments are being combined to allow microsurgery within the eye at a resolution not previously attainable in ophthalmology.  This may open up a new range of surgical approaches to cutting troublesome membranes or vessel compressing tissues in a host of retinal diseases.

A new type of glaucoma drainage surgery is under development. Microscopic drainage tubes “microfistulas” are implanted in the eye to increase the outflow of fluid from the eye to restore normal pressure within the eye.  High pressure within the eye is a major risk factor in glaucoma, a common sight threatening disease currently requiring life long medication to lower the pressure within the eye.  The novel aspect of our surgical approach is that the implantation is achieved without disruption of the overlying tissue at the drainage site, and the biocompatible implant dissolves with time leaving a clear drainage pathway.

The major source of funding for our work is obtained from competitive grants awarded by the National Health and Medical Research Council of Australia (NH&MRC). We have managed to secure continuous NHMRC funding for more than 25 years. Current funding includes several NHMRC Project Grants. Supplementary funding for specific projects when required has been obtained from International funding agencies such as JDFI, and National agencies such as Retina Australia, The Ophthalmic Research Institute of Australia, and Diabetes Australia. Local funding from state government and The University of Western Australia provides much valued infrastructure support. Collaboration with industry partners provides further funding for projects with commercial potential.

The Physiology and Pharmacology Centre offers a very dynamic environment for the training of young scientists, clinicians, and engineers.  The world-class facilities of the Lions Eye Institute, and the presence of many internationally competitive researchers offers many opportunities for post graduate and post doctoral studies.

Postgraduate Positions Available:

  • Retinal Mitochondrion Physiology
  • Laser Interaction with Tissue
  • Drainage Pathways following Filtration Surgery
  • Spectroscopic Monitoring of Retinal Metabolism
  • Tissue Pressure within the Optic Nerve
  • The Physiology of Central Vein Occlusion
  • New Techniques for Treatment of Branch Vein Occlusion

Team Members

Professor Dao-Yi Yu (Director)
Professor Ian McAllister
Professor Stephen Cringle
Professor William Morgan
Associate Professor Er-Ning Su
Assistant Professor Paula Yu
Associate Professor Sarojini Vijayasekaran
Mr Dean Darcey
Ms Kathryn Morgan
Dr Chandra Balaratnasingam
Mr Graeme Hewitt
Mr Fraser Cringle

Students

Dr Min Kang
Dr Priscilla Tan
Dr Geoffrey Chang
Dr Naeem Fatehee

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