Centre projects

Centre Projects

1 Neural mechanisms of stability in visual perception
2 Scientific basis for novel therapies for photoreceptor degenerations
3 Structure and function of the primate macula
4 Oxygen metabolism and retinal function of the fovea using pigeon as a model
5 Advanced multifocal analysis of the visual system with applications to blinding diseases
6 How animals see the world
7 The evolution of trichromatic colour vision in marsupials
8 Mid-air collision avoidance in honeybees
9 Biorobotics: From animals to machines and back
10 Role of complement in retinal degenerations, and targeted treatment strategies


Neural mechanisms of stability in visual perception

Theme/area:     Visual processing and robotics / understanding
CIs:         CWG Clifford1, MR Ibbotson2, S Solomon1   (1U Sydney, 2ANU)
Objectives:         What are the mechanisms that allow us to generate stable, robust and reliable hypotheses about the visual world, even though we have only access to a jittering image of it? Stable representations of the visual world are essential for making decisions about future actions.
Description:       Fundamental to the operation of the visual system is the ability to extract invariant attributes of the environment from the retina image. We do not perceive the world around us as moving or distorted when we make saccades with our eyes even though the image is rapidly smeared across the retina about three times per second.  Similarly our perception of colour is also largely invariant to changes in lighting that occur throughout the day and as we move from one location to another. These remarkable levels of visual stability are achieved despite the fact that the underlying computational units, neurons, exhibit high levels of noise. We will use a combination of fMRI, eye-movement monitoring, neurophysiology, two-photon imaging and intrinsic optical imaging to study the neural activity that must provide these representations.

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Scientific basis for novel therapies for photoreceptor degenerations

Theme/area:     Blinding diseases  /  Understanding and Application
CIs:         J Stone1, DY Yu2, SJ Cringle2   (1U Sydney, 2UWA)
Objectives:         To determine the neuroprotective and therapeutic potential of normobaric hyperoxia, dietary supplements, photobiomodulation (PBM) and light restriction in animal models of retinal degenerations. Our work will extend from a fundamental analysis of retinal cell biology to translation-oriented methods, and will interact with clinical trials already commenced.
Description:       We are now defining dose-protection relationships for hyperoxia, dietary supplements and PBM. These studies stem from our gene microarray analysis of light damage, and PBM and supplement-activated pathways. We have also shown that, at any age, the edge of retina is under oxidative stress, creating stress-related gradients in morphology, photoreceptor stability, morphology and structural integrity. Therefore we are examining stress gradients in the foveal region of older human retinas, both normal and in early stage macular degeneration (AMD). We are also translating our in vivo models to in vitro assays of neuroprotection. Another major objective is to develop widely applicable neuroprotective therapies for still-intractable blinding diseases.

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Structure and function of the primate macula

Theme/area:     Blinding Diseases / Understanding
CIs:         SJ Cringle1, U Grünert2, PR Martin2, JM Provis3, S Solomon2, DY Yu1   (1UWA, 2U Sydney, 3ANU)
Objectives: This study will produce valuable pilot data to leverage larger funding from other sources. To gain better understanding of the macula by studying (1) the relationship between vascular network and neurons, and (2) whether genes control blood vessel density in the macula of normal donor eyes and aged eyes with retinal diseases such as glaucoma and macular degeneration.  We will also obtain pilot data linking oxygen consumption to visual stimulation in marmoset retina.
Description:              The fovea and surrounding macula is responsible for high acuity and colour vision. However, the factors which make the macula vulnerable to blinding disease are poorly understood. This proposal builds on the expertise of 3 groups - in retinal circuitry and nerve cell activity (Sydney node), microvascular anatomy (Perth node) and development and gene expression (ANU node) - to better understand the biology of the fovea and macula, and its role in the onset of macular disease. We will combine our expertise in microperfusion, fixation and staining (initially at the Perth node), visual stimulation and immunochemistry (Sydney node), retinal microvasculature (Perth node) and gene expression (ANU node). The unique aspect of this proposal is the development of common anatomical analyses for marmoset and donor human eyes. This will enable hypotheses to be linked to observations of anatomical and gene expression variation in normal and diseased eyes.

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Oxygen metabolism and retinal function of the fovea using pigeon as a model

CIs:         DY Yu1, JM Provis2, SJ Cringle1, T Maddess2, KM Bumsted-O’Brien2   (1UWA, 2ANU)
Project title:      Oxygen metabolism and retinal function of the fovea using pigeon as a model
Theme/area:     Blinding diseases.   Understanding
Objectives:         To gain a better understanding of cone metabolism and function using the cone rich retina of the pigeon. It is very difficult to separate metabolic requirements of rods and cones in the mammalian retina.  The pigeon thus offers a rare opportunity to perform in vivo assessment of retinal metabolism and function in a cone dominated retina.
Description:       Cone cells permit us to see in daylight, and their energy demand is crucial. However, we lack detailed knowledge of cone function and energy demands.  There are significant advantages in using the pigeon fovea as a model for studying visual function and energy metabolism: (1) a layered structure similar to human fovea, (2) an anangiotic retina 1.5 to 2 times thicker than in human, and (3) a cone dominated fovea. These advantages allow us to reliably measure the intraretinal oxygen distribution without the influence of retinal vasculature allowing us to determine the energy metabolism in specific retinal layers, using our oxygen sensitive microelectrode techniques, under controlled light and oxygen conditions.  Complementary histological techniques will be used to provide supportive evidence for high oxygen demand in specific retinal layers. Optical coherence tomography will be used to quantify changes in retinal thickness with pigeon age.

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Advanced multifocal analysis of the visual system with applications to blinding diseases           

Theme/area:     Visual processing / Understanding (1a)  and  Blinding diseases / Application (2b)
CIs:         T Maddess1, AC James1, TD Lamb1, PR Martin2, JM Provis1   (1ANU, 2U Sydney)
Objectives:         The project will develop our methods for multifocal analysis of visual systems using evoked potentials, evoked magnetic fields, functional MRI and pupillography. In one aspect we will focus on quantifying nonlinear processes and interactions across visual field. In another aspect we seek to improve multifocal methods for diagnosing and monitoring diseases affecting vision including: glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and multiple sclerosis. Pupillographic multifocal methods are of particular interest.
 Description:      Multifocal analysis refers to concurrent presentation of sequences of stimuli at multiple locations in the visual field, and the analysis and characterization of the resulting compound responses. Within the Centre these methods are the basis for the studies on human visual cortex using visual evoked potentials (VEP) evoked magnetic fields (VEF) and functional MRI (James and PI Vanni), utilizing the world-class neuroimaging facilities provided to the Centre by the Helsinki University of Technology, and in microelectrode studies of insects (van Kleef, James) and anesthetized cats (Ibbotson, James, van Kleef) and primates (Martin). Multifocal methods also form the basis of the diagnostic technology (Maddess, James): the TrueField Analyser (TFA), designed and built with the Centre’s commercial partner Seeing Machines, and in collaboration with CIs Provis and Lamb, and PIs Essex and Lueck. Proof of concept studies for TFA variants for glaucoma, macular degeneration, diabetic retinopathy and multiple sclerosis are underway.

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How animals see the world      

CIs:         PR Martin1, JM Hemmi2, MV Srinivasan3, J Zeil2   (1U Sydney, 2ANU,  3UQ)
Objectives:         We are developing a web-based research, outreach and education tool that allows users to learn about how animals with their diverse visual systems see the world - in terms of colour and polarization sensitivity and variations in visual acuity.
Description:       The public web-resource will show (1) how the world appears through the visual systems of dichromatic, trichromatic and tetrachromatic animals, both vertebrate (wallabies, dunnarts, possums, marmosets) and invertebrates (honeybees, ants, fiddler crabs); (2) how the world appears through the non-uniform sampling arrays of honeybees, ants and fiddler crabs, some fish and marsupials; (3) how the world appears through the eyes of animals that operate under low light conditions and/or are sensitive to the plane of polarization of light (e.g. honeybees, ants, fiddler crabs, possum); (4) what animals with different visual systems see when they perform different tasks or are confronted with different problems, as when honeybees fly through narrow gaps or execute landings, fiddler crabs detect predatory birds or when ants, wasps or honeybees execute complex navigational tasks.

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The evolution of trichromatic colour vision in marsupials        

CIs:         JM Hemmi1, PR Martin2, U Grünert2, K Valter1(1ANU , 2U Sydney)
Objectives:         To determine how some marsupials achieve trichromacy through analysis of their retinal anatomy, their colour sensitivities and their behavioural colour discrimination abilities. The project will compare the colour vision system of marsupials to other mammalian di- and trichromats and develop a framework for understanding  the evolution of marsupial colour vision. Marsupials are the only mammals other than primates reported to have three cone types and thus trichromatic colour vision. The mechanism leading to trichromacy, however, appears to be different.
Description:       Several marsupial species have been shown to possess three cone populations. The opsin that is expressed in one of the three cone types, however, is unknown. For several reasons we believe that marsupials achieve trichromatic colour vision using cones that express rhodopsin, normally found in night vision giving rod cells. The project will concentrate on investigating the colour vision system of the fat-tailed dunnart (diurnal), the brush-tail possum (nocturnal, but colour vision confirmed) and compare them to the dichromatic tammar wallaby. Techniques employed include: in-situ hybridization and immunohistochemistry (Grünert, Valter, Hemmi), behaviour (Hemmi), adptive optics imaging of the retinas (Martin, Grünert and PI Metha), and numerical modeling (Hemmi and PI Vorobyev).

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Mid-air collision avoidance in honeybees

Theme/area:     Visual processing and robotics / Understanding
CIs:         MV Srinivasan1(1UQ)
Objectives:         There has been much interest by both biologists and engineers working on autonomously flying vehicles about how flying insects detect and chase other flying insects, or how certain insects camouflage their own motion to avoid detection by others. However, we know very little about whether flying insects actively avoid colliding with each other. The aim of this study is to investigate whether honeybees avoid mid-air collisions, and if so, to understand how. This will be the first study of mid-air collision avoidance in flying insects. The research could thus open up a new area of investigation in animal behavior and reveal valuable information for robotics.

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Biorobotics: From animals to machines and back

Theme/area:     Visual processing and robotics / Application
CIs:         MV Srinivasan1, J Zeil2    (1UQ, 2ANU)
Objectives:         This study has two aims: (i) To build a fully autonomous fixed-wing aircraft.  (ii) To discover the basis of autonomy in navigating Arthropods with particular emphasis on obstacle avoidance and view-based homing, abilities that are crucial for realizing autonomous navigation in cluttered natural environments. Robotics is turning increasingly to biology for inspiration in developing algorithms for vision and navigation that are robust. The proposed research will also provide much-needed robotic platforms for testing insect-inspired vision and navigation algorithms.
Description:       We will continue the program of work that we have been pursuing to develop a fully autonomous fixed-wing aircraft, based on principles of visual guidance in insects. Our goals over the next 3 years will be (a) automated obstacle avoidance (b) automated landing (c) automated takeoff and (d) a fully automated mission comprising takeoff, way-point based navigation to a specified location, acquisition of prescribed visual information at that site, return to origin, and automated landing. We will also investigate the strategies used by flying and walking animals when they encounter obstacles in their path. Of particular interest are the strategies used by insects to acquire and use goal-related visual memories for navigation.

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Role of complement in retinal degenerations, and targeted treatment strategies

Theme/area:     Blinding diseases / Understanding, and Application
CIs:         K Valter1, JM Provis1   (1ANU)
Objectives:         To establish a time course of complement activation and its relationship to cell death occurring during retinal degenerations. Once the role of complements is established, we will trial different therapeutic interventions aiming to block this activation, to treat or prevent degeneration.  Thus this project aims to understand the pathology of age-related macular degeneration (AMD), the leading cause of blindness among the aged population of the Western World. AMD poses a huge burden on the health system and so is now a national research priority.
Description:       Age-related macular degeneration has been linked to the mis-regulation of the complement system, a major component of the innate immune response. The initiating event that leads to the activation of the complement cascade however is still unknown. This proposal examines whether photoreceptor (PR) damage or death activates the complement cascade, which, if not controlled, can lead to inflammation and further damage to surviving PR’s and surrounding tissue. We will investigate inhibition of the complement system in two models of retinal degenerations: 1) light-induced retinal degeneration, and 2) a transgenic animal. Inhibition will be via complement control proteins, steroids and a new method being developed with a commercial partner.

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