School of Optometry and Vision Sciences

Research Interests

My research focus is on the role of mitochondrial dynamics in the pathophysiology of neurodegenerative disease. My focus has been inherited optic neuropathy, with an emphasis on generating model systems to study retinal ganglion cell (RGC) loss and inner retinal degeneration, which occurs as a primary phenomenon in a number of human genetic diseases.

We are studying RGC loss and rescue in vitro and in vivo, and the sequelae of this neurodegeneration on inner retina. To this end, we have been studying retinal ganglion cell lines and primary RGCs, utilising siRNA to explore the effect of opa1 knockdown on cell viability and the mechanism of cell death. We are also exploring the role of neuroprotective agents. OPA1 is known to bind to inner mitochondrial membrane, and when mutated it is believed that the normal balance of mitochondrial fusion and fission is disturbed and programmed cell death is initiated by the loss of mitochondrial membrane potential and the release of cytochrome c. We are also investigating the role of the OPA3 gene in both RGC loss and cataract formation. OPA3, like OPA1, is thought to have a role in mitochondrial membrane dynamics, and when mutated in the human, a complex neurodegenerative disease, comprising optic neuropathy secondary to RGC loss, cataract and neuromuscular degeneration, arises. I continue to recruit patients with inherited optic neuropathy for genetic screening.

Figure 2. Dendritic tree arborisation of a single Opa1+/- retinal ganglion cell from murine retina labelled by diolisthics.

Figure 3. Electron micropgraph of mitochondria from a retinal ganglion cell carrying a mutation in OPA1 causing loss of organisation of cristae in the mitochondria (arrow)

Research Alumni

Post- doctoral Research Associates

Dr Vanessa Davies
Dr Ruby Grewel
Dr Andrew Hollins
Dr Kate Powell

Professional Training Scheme

Rebecca  Thirgood

Technical Assistant

Elaine Taylor

Summer Students

2005

Marios Sarros. Welcome Trust Summer Scholarship. Mutation screening in inherited optic neuropathy.

2006

Yip WanFen. Welcome Trust Summer Scholarship. Histology of the eye in an opa1 mutant mouse.

2007

Laura Byrne. Welcome Trust Summer Scholarship. Longitudinal phenotyping in ADOA and new aspects of the phenotype- circadian rhythm and cognitive function.

2011

Amanda Mui.  Drp1 visual and neurological phenotyping.

2012

Rebecca Watts. Nuffield Summer Studentship. Mitochondrial Eye Disease.

Grant funding

Invited Lectures

2008

• OPA1 and inherited neuropathy. ARVO Genetics Workshop, Fort Lauderdale, Florida, USA
• Mentoring and the Clinician Scientist Experience. Academy of Medical Sciences Meeting, Taunton
• Genetics of optic nerve disease. Midlands Ophthalmological Society, Leicester
• Three Blind Mice. British Eye Study Group, Saunton Sands, Devon

2009

• OPA1 and OPA3 Mice in neurodegeneration. Cardiff Neuroscience Centre, Cardiff University
• Mouse models of inherited optic neuropathy. Keystone Symposium on Mitochondrial Dynamics and Physiology. Whistler, British Columbia, Canada
• Genetics of Optic Atrophy. The Royal College of Ophthalmologists Annual Congress, B’ham

2010

• Nuclear gene OPA1 and OPA3 and mitochondrial function in optic neuropathy. Leeds Institute of Molecular Medicine
• Mitochondrial shaping proteins in neurodegenerative diseases of the eye. Oxford/ Bristol/ Cardiff Alliance Meeting, Oxford
• Mitochondrial plasticity and inner retinal degeneration. Vision Research Meeting, Insights into retinal function, repair and angiogenesis, Bristol
• Opa1- a story of mitochondrial plasticity and inner retinal degeneration. Tennent Institute of Ophthalmology, Glasgow

2011

• Assessment and diagnosis of optic neuropathies. Clinical Neurology Meeting, University Hospital of Wales
• Personal experience of mentoring. Academy of Medical Sciences Mentoring Symposium, Cardiff
• A clinical academic career. Women Professors Forum, Cardiff University

2012

• Mitochondrial eye disease. UK Eye Genetics Group. University of Bristol
• Mouse models of mitochondrial optic neuropathy. For: SIG Mitochondrial dysfunction and retinal ganglion cell loss in optic neuropathies – from disease mechanisms to therapeutic strategies. ARVO, May 2012
• Optic neuropathies. For: European Professors of Ophthalmology, Leuven, June 2012

Research Collaborators:

International

Professor Anne A. Knowlton, M.D., Professor of Medicine and Medical Pharmacology, Molecular & Cellular Cardiology, University of California, Davis, California, USA.

Professor Don Newmeyer, PhD, La Jolla Institute for Allergy and Immunology, La Jolla, CA , USA.

Professor Peter Nuernberg, PhD, Cologne Centre for Genomics, University of Cologne, Germany.

National

Dr Patrick Yu-Wai-Man, MRC Clinician Scientist, Mitochondrial Research Group, The Medical School
University of Newcastle upon Tyne,

 Professor Patrick Chinnery, PhD FRCP, Wellcome Senior Fellow in Clinical Science, Professor of Neurogenetics and Honorary Consultant, Mitochondrial Research Group, The Medical School
University of Newcastle upon Tyne

Professor Ron Douglas, Professor of Visual Science: Deputy Head of Department, City University London

Professor Jo Poulton, PhD MRCP, Professor of Mitochondrial Genetics, John Radcliffe Hospital, University of Oxford

Professor Tim Wells, PhD, School of Bioscience, Cardiff University.