The Provis Group - Gene expression in the human macula

The primate retina, including humans, has a unique region in the central retina that is specialized for high-resolution vision. At the centre of the macula is the highly specialized, fovea centralis. Without proper function of this small region of the retina, humans are legally blind. The disease, age-related macular degeneration, is a form of neural degeneration that specifically targets the macula. But why the macula? To answer this question we recently undertook a series of studies that have identified the genes that are differentially expressed in the macula during development. We now aim to examine how the expression of these genes varies over a lifetime. To do this we are collecting human donor retinas from 2 Eye Banks in Australia. Using these we can establish the levels of expression of genes of interest in juvenile, young adult and aged adult eyes, as well as in some pathologies, including AMD.

The role of the immune system in photoreceptor degeneration

Age-related macular degeneration is the most common cause of untreatable blindness. Recent studies have shown a clear link between genetic variants of genes involved in the complement cascade, and onset and progression of the disease. It appears that failure to down-regulate complement is a major factor in the progression of macular degeneration. But why is this component of the immune system activated in at-risk individuals? To answer this question we are investigating the time-course of expression of complement-related genes in rodent models of retinal degeneration. The findings to date show that complement genes are upregulated early in the time-course of experimental retinal degeneration and that they are highly associated with progression of degeneration, after the initial period of insult. Ongoing experiments are aimed at using techniques to inhibit complement expression and to monitor the effects on progression of retinal degeneration in these models.

The effect of 670nm light irradiation on growth and development

In the retina, exposure to 670nm red light has been shown to be neuroprotective against methanol toxicity, light damage and oxygen toxicity. 670nm light has also been shown to increase wound healing, cell proliferation, migration, attenuate degradation and promote tissue growth in mammals, by increasing in the function and efficiency of cytochrome oxidase. The aim of this project is to study the effect of 670nm light on the developing rodents to see if a 670nm light has any effect on development, including changes to the eye, brain, liver, kidney, spleen, lungs and heart. These experiments will provide a framework to validate the safety of using 670nm light as a treatment to assist with human developmental diseases. The focus of the study will be on changes associated with eye, in order to develop a treatment strategy for the eye disease retinopathy of prematurity (ROP), which is a retinal vasculature disease that affects premature babies as a result of being exposed to increased oxygen in the humidicrib.




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