Fletcher laboratory: Visual neuroscience

Research Overview

The Visual Neuroscience laboratory is interested in:

  1. Why photoreceptors die during retinal degeneration, including retinitis pigmentosa (RP) and Age-Related Macular Degeneration (AMD)
  2. Ways of replacing lost photoreceptors or slowing photoreceptor death in inherited retinal degenerations
  3. The role of glia in retinal disease

Diseases of the retina that 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:

1. Retinal degenerations, including Age-Related Macular degeneration

Retinal degenerations are a family of hereditary diseases that cause a gradual loss of photoreceptors leading to 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 diseases such as Age-Related Macular Degeneration (AMD), 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 pre-clinical 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.

2. 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 overt 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.

Staff

Dr Ursula Greferath, Senior Research Officer
Dr Kirstan Vessey, Senior Research Officer
Dr Andrew Jobling, Senior Research Officer
Dr Joanna Phipps, ARC DECRA Fellow
Dr Felix Aplin, Research Officer
Dr Tracy Ho, Research Officer
Ms Lidia Trogrlic, Research Assistant
Mr Gene Venables, Research Assistant
Mr Sam Mills, PhD student
Mr Philipp Guennel, PhD student
Ms Kiana Kakavand, PhD student
Mr Gudmundur Jonsson, PhD student
Mr Mario Huynh, Masters student
Mr Michael Dixon, Honours student

Collaborators

Professor Michael Kalloniatis, Centre for Eye Health and Dept. Optometry, UNSW
Professor Richard Kramer, Molecular & Cell Biology, UC Berkley

Funding

National Health & Medical Research Council of Australia
Australian Research Council
Retina Australia
American Health Assistance Foundation
Commercial contracts

Research Publications

See 'Download Research Publication' below for a list of Professor Erica Fletcher's publications (2010 - 14).

  1. Vessey KA, Wilkinson-Berka JL, Fletcher EL. Characterization of retinal function and glial cell response in a mouse model of oxygen-induced retinopathy. J Comp Neurol 2011; 519:506-527.
    ERA=A*; cited 38 times, averaging 9 citations per year. This paper characterized in detail the glial and neuronal changes in a mouse model of oxygen induced retinopathy. In particular we were able to correlate very precisely gliotic change with vascular pathology of the outer retina.
  2. Ly A, Yee P, Vessey KA, Phipps JA, Jobling JA, Fletcher EL. Early inner retinal astrocyte dysfunction during diabetes and development of hypoxia, retinal stress and neuronal functional loss. Invest Ophthalmol Vis Sci 2011; 52:9316-9326.
    ERA=A+ cited 26 times, averaging 6 times per year; was in the top ten of all papers downloaded from IOVS in the 12 months following publication. This paper correlated glial, vascular and neuronal changes at an early stage of diabetes.
  3. Fletcher EL, Phipps, JA, Ward MM. The renin-angiotensin system in retinal health and disease: its influence on neurons,glial and the vasculature. Prog Ret Eye Res 2010; 29: 284-311.
    Cited 53 times; averaging 10 citations per year. This invited review, published in the highest ranked journal in vision, provided the most comprehensive account of the role of the renin-angiotensin system in the retina.
  4. Vessey KA, Fletcher EL.  Rod and cone pathway signalling is altered in the P2X7 receptor knockout mouse. PLoSOne 2012; 7: 290-305.
    ERA=A; cited 18 averaging 6 times per year. This paper characterized in detail the P2X7 knockout mouse and showed that this receptor contributes to retinal signalling.
  5. Jobling AI, Guymer RH, Vessey KA, Greferath U, Mills SA, Brassington KH, Luu CD, Aung KZ, Trogrlic L, Plunkett M, Fletcher EL. Nanosecond laser therapy reverses pathological and molecular changes in age related macular degeneration without retinal damage. FASEB J 2015; 29: 696-710.
    This study was the first to identify the potential mechanism by which a novel ophthalmic laser reduces signs of age related macular degeneration. It was widely reported in the lay press, was the subject of a patent application and has received considerable attention.

Download Research Publication [PDF]