Fletcher Lab - Overview
We Are Interested In:
(i) How the retina operates under normal conditions.
(ii) The underlying causes of diabetic retinopathy and ways of preventing the progression of this disease.
(iii) Why photoreceptors die during retinal degeneration and Age-Related Macular degeneration, and ways of slowing photoreceptor death.
(iv) Ways of replacing lost photoreceptors during retinal degeneration.
Diseases of the Retina Cause Blindness
Retinal diseases are a major cause of blindness in the Western world. Few treatments are currently available, largely because the underlying mechanisms of disease are not well understood. Our laboratory studies two broad classes of retinal disease:
- Retinal vascular diseases including Diabetic retinopathy: Diabetes affects 3.8% of the population of Australia, at an annual cost of AUS$1 billion dollars. Diabetic retinopathy is a common complication associated with diabetes and is the leading cause of blindness in those under 65 years of age. Some 10% of all diabetics experience vision threatening retinopathy. One of the major reasons for vision loss is the growth of new blood vessels in the retina (neovascularization). Although a great deal of attention has focussed on the vascular changes associated with diabetes, it is now emerging that changes in neuronal and glial cell function often occur prior to vascular abnormalities. Understanding the link between glial cell dysfunction and changes in vasculature is vital for gaining a better understanding of the pathogenesis of diabetic retinopathy. The major thrust of our work is understanding the changes in the retina that lead to neovascularization. We also examine whether novel treatments prevent or slow vision loss.
- RETINAL DEGENERATIONS including Age-Related Macular Degeneration: a family of hereditary diseases that causes gradual loss of photoreceptors and consequently blindness. These diseases occur in around 1:5500 people, but 1:50 are carriers. We are examining the mechanisms of photoreceptor death and whether specific treatments ameliorate or slow the loss of photoreceptors.
Understanding how photoreceptors die is of relevance to another disease called Age-Related Macular Degeneration, which is one of the leading causes of blindness especially in older people. Photoreceptor death and abnormal growth of blood vessels into the retina are major contributors to blindness in this disease. We use animal models to understand the underlying mechanisms involved and whether treatments slow the progression of disease.
Our ultimate goal is to develop ways of slowing photoreceptor death and also to investigate ways of replacing lost photoreceptors.
Animal Models Currently Available
We use the following animal models of eye disease to understand the pathophysiology of diabetic retinopathy, retinal degeneration and Age-Related Macular Degeneration:
- Diabetes: STZ induced diabetes in rat and mice
- Retinal degeneration: light induced damage, rd1 mice; rd1/P2X7null mice
- Age-related Macular Degeneration: MCP-1null mice