Research

Understanding retinal function is fundamental to determining how the visual system performs in healthy and diseased states. Many aspects of normal retinal function, such as the framework by which the retina processes visual information in neural networks, are at least partially known. However, there are several components of visual function and processing that remain unclear.

The formation of antagonistic centre-surround receptive fields in ganglion cells, the output neurons of the retina, is an example of how activity in relatively simple synaptic circuits can produce the response archetypes responsible for visual system function. This complex processing of a "simple" stimulus allows us to detect contrast and edges in our visual environment.

Many diseases of the retina that lead to visual impairment or blindness are associated with genetic or environmentally induced conditions culminating in the degeneration of neurons. Regardless of origin, pathophysiological changes in the retina are in many cases associated with over-activation of synaptic mechanisms, receptors and ion channels—the same processes that underlie the orderly processing of visual information in healthy retinas. Thus, a better understanding of these processes will provide a framework for the development of new therapeutics.

A general strategy taken in the retina has receptive fields determined through the synaptic integration of visual information in direct (or centre) neural pathways and lateral (or surround) pathways.

Glutamate typically carries the flow of information between neurons in the direct pathway of visual system, that is, from the photoreceptors to bipolar cells and then to ganglion cells. Lateral interactions of horizontal cell and amacrine cell networks that occur through the actions of a host of neurotransmitters and neuromodulators are less well understood.

While the bulk of neuromodulation and receptive field formation is mediated by synaptic circuits in neural networks, glial cells too have been implicated in the modulation of retinal performance.

The Retina and Optic Nerve Research Laboratory investigates a full spectrum of mechanisms involved in receptive field formation.

Excitatory amino acids, such as glutamate, are also key mediators in excitotoxicity and are the targets in many neuroprotection strategies. Diseases such as glaucoma involve excitatory synaptic circuits, which may in turn involve neuromodulator systems.

Improved animal models of these diseases are providing important knowledge of the mechanisms underlying receptive field formation and visual function, an outcome of paramount importance for the diagnosis of disease, the design of neuroprotective therapies and the measurement of their efficacy.

The same synaptic mechanisms that mediate the formation of normal synaptic circuits and receptive fields may contribute to cellular damage.

Ongoing work in the Retina and Optic Nerve Research Laboratory has advanced the knowledge of receptive field interpretation, retinal disease progression and identified novel therapeutic targets, which contribute to translational research for clinical applications.