Prof Marcela Votruba
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)
INTERNATIONAL INNOVATION - Investigations into genes associated with mitochondrial plasticity; research that will help to inform understanding of eye disease.
Post- doctoral Research Associates
Dr Vanessa Davies
Dr Ruby Grewel
Dr Andrew Hollins
Dr Kate Powell
Professional Training Scheme
Marios Sarros. Welcome Trust Summer Scholarship. Mutation screening in inherited optic neuropathy.
Yip WanFen. Welcome Trust Summer Scholarship. Histology of the eye in an opa1 mutant mouse.
Laura Byrne. Welcome Trust Summer Scholarship. Longitudinal phenotyping in ADOA and new aspects of the phenotype- circadian rhythm and cognitive function.
Amanda Mui. Drp1 visual and neurological phenotyping.
Rebecca Watts. Nuffield Summer Studentship. Mitochondrial Eye Disease.
|2003- 2007||MRC Clinician Scientist Fellowship (£750,000 over 4 years). M Votruba. Sponsor M Boulton.|
"The pathophysiology of inherited optic neuropathy".
|2005||Wellcome Trust Summer Studentship (£1800). M Votruba.|
"Human mutations in optic atrophy". (Marrios Sarros)
|2006-2009||MRC Research Grant (£200,005 over 3 years). M Votruba, M Boulton, M Wride.|
"OPA3: a novel gene and mechanism in cataractogenesis". Funding RA1A
|2006-2008||RoFAR Research Award (£86,207 over 2 years). M Votruba.|
"Erythropoietin neuroprotection in retinal neurodegeneration". Funding RA1A
|2006||Wellcome Trust Summer Studentship (£1360). M Votruba.|
“Morphological assessment of retina in models of hereditary optic neuropathy.” (Yip WanFen).
|2007-2009||BBSRC Research Grant (£255,955 over 2 years). J Morgan, W Drexler, M Votruba, M Wride.|
“In vitro detection of neuronal programmed cell death by ultrahigh resolution optical coherence tomography.”
|2007||Wellcome Trust Summer Studentship (£1400). M Votruba.|
“Longitudinal phenotyping in ADOA and new aspects of the phenotype- circadian rhythm and cognitive function.” (Laura Byrne).
|2008-2011||MRC Research Grant (£508,864 FEC over 3 years). M Votruba.|
"Mitochondrial shaping proteins in models of optic neuropathy ". Funding RA Grade 6 and Technician Grade 4.
|2012||Nuffield Foundation Science Bursary for Schools & Colleges: awarded to Rebecca Watts, Supervisor: M Votruba. “Histological assessment of tissue from Opa1 mutant mouse.” £1200|
|2012-2013||Fight for Sight Dr Hans and Mrs Gertrude ~Hirsch Grant Award (£15,000). M Votruba. “Find the missing genes: next generation sequencing to accelerate the pace of disease gene discovery in patients with inherited optic neuropathy”.|
|2013-2014||Thermo Fisher Inspire Award (£5000). Mechanism of neurodegeneration in mice with mitochondrial dysfunction.|
|2013-2016||Fight for Sight Research Studentship (£100,000). M Votruba. “Light therapy for optic neuropathy”.|
- 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
- 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
- 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
- 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
- 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
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.
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.