Yr Athro Marcela Votruba
Pennaeth yr Ysgol
- votrubam@cardiff.ac.uk
- +44(0)29 2087 0117
- Fax:
- +44 (0)29 2087 4859
- Room 1.15, Maindy Road, Optometreg a Gwyddorau'r Golwg , Heol Maendy, Cathays, Caerdydd, CF24 4HQ
- Sylwebydd y cyfryngau
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwg
Career Overview
The work of my laboratory focuses on mitochondrial fusion/ fission genes and neural plasticity in human eye disease. This springs from work on the pathophysiology of inherited optic neuropathy. We are currently investigating new therapeutic targets for retinal ganglion cell loss, inner retinal degeneration and repair. We are also looking at mitochondrial shaping proteins in retinal degeneration in disease and ageing. We have been interested in the roles of fusion/ fission genes, such as Opa1 and Opa3. 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. 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.
As part of my role as a Clinician Scientist, I also recruit patients with inherited optic neuropathy for genetic screening and I run a Retinal Clinic and a Genetic Eye Clinic, at the University Hospital of Wales.
Research Interests
My goals are aimed at developing a deeper understanding of inherited eye disease and ultimately utilising my position as a clinical ophthalmologist to drive the application of translational research in this area. My primary research interest is the pathophysiology of hereditary retinal and optic nerve diseases. I am currently investigating inherited optic neuropathies, which are a pure model of isolated retinal ganglion cell loss. They demonstrate a central role for mitochondria and show some progressive neurodegeneration. Retinal ganglion cells are the cells that make up the nerve of vision, taking impulses from the retina to the brain. Autosomal dominant optic atrophy is the commonest inherited optic neuropathy. It is caused by mutations in the OPA1 gene, leading to visual loss, which first starts in children and young people. Clinical understanding of the disease is poor, although we have clinical and some pathological evidence that retinal ganglion cells are deficient in the eyes of patients. There is no treatment available. Conventional clinical or research strategies have yet to make any clinical impact on this state of affairs. The mechanism of action of the mutant protein OPA1 is not known, but clues exist suggesting that the shape or function of small organelles in the cell, mitochondria, may be involved. Mitochondria are important in generating energy in the cell. Following on from our work to characterise the disease phenotype and clone the disease gene, my group has analysed the spectrum of mutations in the OPA1 gene and genotype/ phenotype correlations. We have performed functional and expression studies of the OPA1 gene and assessed its wider role in inherited optic neuropathy and we are developing model systems to explore the mechanisms and pathways of RGC loss.
Bywgraffiad
University Education
1981-1984 Undergraduate Pre-Clinical Studies:The Queen$acirc; s College, University of Oxford
1984-1987 Clinical Studies: Green College, University of Oxford Medical School
Academic And Professional Qualifications
1984 BA Hons 2:1 (Oxon)
1987 MA (Oxon)
1987 BM BCh (Oxon)
1989 Primary FRCS
1990 Optics & Refraction, Royal College of Ophthalmologists, London
1991 MRCOphth, London
1992 FRCOphth, London
1999 PhD, University College, London
2000 CCST (December 2000), Royal College of Ophthalmologists, London
Awards And Honours
Undergraduate Distinctions
1981 Open Scholarship, The Queen$acirc; s College, Oxford
1984 First Class Hons. Dissertation, Oxford University
1987 Final Year Clinical Prize: Green College, Green College, Oxford
Postgraduate Prizes
1996 The Royal Society of Medicine: Ophthalmology Section- Registrars$acirc; Meeting: First Prize (Awarded for the Best Paper at Annual Training Meeting)
Research Fellowships
1994 Guide Dogs for the Blind Association Research Fellowship
1998 Wellcome Trust Vision Research Training Fellowship
2002 Frost Research Fellowship
2003 MRC Clinician Scientist Fellowship
Appointments
Present Substantive Appointment
Aug 2011 Professor and Hon. Consultant in Ophthalmology, Cardiff University and The Cardiff & Vale NHS Trust, University Hospital of Wales.
Previous Substantive Appointments
April 2003- October 2003 Full-time Consultant in Medical Retina, Moorfields Eye Hospital, Service Lead for Audit & Clinical Governance, Service Lead for ARMD Research.
Oct 2003- Sept 2007 MRC Clinician Scientist Fellow & Hon. Consultant
Senior Lecturer, Cardiff University and The University Hospital of Wales.
Teaching
Undergraduate Optometry Teaching
I lecture to final year Optometry students on the Abnormal Ocular Conditions Course.
Postgraduate Teaching in Ophthalmology
2009
- Neuro-ophthalmology case. Visual recovery in Leber$acirc; s hereditary Optic Neuropathy. Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff
2010
- Practical genetics of optic atrophy. Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff
- Invited Judge for Vision Research Day, Cardiff.
2011
- Retinal ganglion cell dendropathy. Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff.
- Invited Judge for Vision Research Day, Cardiff.
2012
- Mitochondrial eye disease, Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff.
Administration
I sit of the School of Optometry & Vision Sciences Research Committee (2007- present). Since 2012 I have been Deputy Director of Research and am Chair of the REF Working Group. I am also a member of the Equality & diversity /SWAN ATHENA Committee in OPTOM.
Other Academic Activities
Principal Investigator on the MRC Mouse Eyes & Vision Consortium.
Editorial Board of Acta Ophthalmologica
Editorial Board of the World Journal of Neurology
Guest Editor for Drug Discovery Today: Disease Models (with Prof Ian Jackson, Edinburgh)
External Committees:
UK Eye Genetics Group Steering Committee,
Lead Principal Investigator and co-ordinator of the MRC Mouse Eyes & Vision Consortium.
I am Programme Secretary (2011-2016) of European Association for Vision and Eye Research (EVER). I was the Vice President, 2009-2010, and past Section Chair for Molecular Biology/ Genetics/ Epidemiology on the Board of EVER (2004-2009). I was also the Editor of the EVER eNewsletter, which is published four times per year (2005-2009).
Innovation and Engagement:
I am STEM Net Ambassador and have been into local schools in Bristol to give talks about science and careers in science and medicine (e.g., Redland High school, Bristol, March 2013).
I am a Mentor for two research fellows.
Anrhydeddau a Dyfarniadau
Undergraduate Distinctions
- 1981 Open Scholarship, The Queens College, Oxford
- 1984 First Class Hons. Dissertation, Oxford University
- 1987 Final Year Clinical Prize: Green College, Green College, Oxford
Postgraduate Prizes
- 1996 The Royal Society of Medicine: Ophthalmology Section- Registrars Meeting: First Prize (Awarded for the Best Paper at Annual Training Meeting)
Research Fellowships
- 1994 Guide Dogs for the Blind Association Research Fellowship
- 1998 Wellcome Trust Vision Research Training Fellowship
- 2002 Frost Research Fellowship
- 2003 MRC Clinician Scientist Fellowship
Aelodaethau proffesiynol
Present Substantive Appointment
- Aug 2011 Professor and Hon. Consultant in Ophthalmology, Cardiff University and The Cardiff & Vale NHS Trust, University Hospital of Wales.
Previous Substantive Appointments
- April 2003- October 2003 Full-time Consultant in Medical Retina, Moorfields Eye Hospital, Service Lead for Audit & Clinical Governance, Service Lead for ARMD Research.
- Oct 2003- Sept 2007 MRC Clinician Scientist Fellow & Hon. Consultant Senior Lecturer, Cardiff University and The University Hospital of Wales.
Ymrwymiadau siarad cyhoeddus
I am STEM Net Ambassador and have been into local schools in Bristol to give talks about science and careers in science and medicine (e.g., Redland High school, Bristol, March 2013).
I am a Mentor for two research fellows.
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$acirc; 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 $acirc; from disease mechanisms to therapeutic strategies. ARVO, May 2012
- Optic neuropathies. For: European Professors of Ophthalmology, Leuven, June 2012
2013
- European Neuromuscular Consortium, Naarden, Holland
Opa1 ocular and CNS effects. Mitochondrial Research Group, John Radcliffe Hospital, Oxford
Pwyllgorau ac adolygu
I sit of the School of Optometry & Vision Sciences Research Committee (2007- present). Since 2012 I have been Deputy Director of Research and am Chair of the REF Working Group. I am also a member of the Equality & diversity /SWAN ATHENA Committee in OPTOM.
Other Academic Activities
- Principal Investigator on the MRC Mouse Eyes & Vision Consortium.
- Editorial Board of Acta Ophthalmologica
- Editorial Board of the World Journal of Neurology
- Guest Editor for Drug Discovery Today: Disease Models (with Prof Ian Jackson, Edinburgh)
External Committees
- UK Eye Genetics Group Steering Committee
- Lead Principal Investigator and co-ordinator of the MRC Mouse Eyes & Vision Consortium.
I am Programme Secretary (2011-2016) of European Association for Vision and Eye Research (EVER). I was the Vice President, 2009-2010, and past Section Chair for Molecular Biology/ Genetics/ Epidemiology on the Board of EVER (2004-2009). I was also the Editor of the EVER eNewsletter, which is published four times per year (2005-2009).
Cyhoeddiadau
2022
- Thomas, R. H. et al. 2022. Research priorities for mitochondrial disorders: current landscape and patient and professional views. Journal of Inherited Metabolic Disease 45(4), pp. 796-803. (10.1002/jimd.12521)
2021
- Beirne, K., Freeman, T. J., Rozanowska, M. and Votruba, M. 2021. Red light irradiation in vivo upregulates DJ-1 in the retinal ganglion cell layer and protects against axotomy-related dendritic pruning. International Journal of Molecular Sciences 22(16), article number: 8380. (10.3390/ijms22168380)
- Tribble, J. R. et al. 2021. Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. Redox Biology 43, article number: 101988. (10.1016/j.redox.2021.101988)
- Kim, D., Votruba, M. and Roy, S. 2021. Opa1 deficiency promotes development of retinal vascular lesions in diabetic retinopathy. International Journal of Molecular Sciences 22(11), article number: 5928. (10.3390/ijms22115928)
- Erchova, I., Sun, S. and Votruba, M. 2021. A perspective on accelerated ageing caused by genetic deficiency of the metabolic protein, OPA1. Frontiers in Neurology 12, article number: 641259. (10.3389/fneur.2021.641259)
- Ng, W. S. V. et al. 2021. New avenues for therapy in mitochondrial optic neuropathies. Therapeutic Advances in Rare Disease 2, pp. 1-14. (10.1177/26330040211029037)
2020
- Catarino, C. B. et al. 2020. Real-world clinical experience with Idebenone in the treatment of Leber hereditary optic neuropathy. Journal of Neuro-Ophthalmology 40(4), pp. 558-565. (10.1097/WNO.0000000000001023)
- Varricchio, C., Beirne, K., Aeschlimann, P., Heard, C., Rozanowska, M., Votruba, M. and Brancale, A. 2020. Discovery of Novel 2-Aniline-1,4-naphthoquinones as potential new drug treatment for Leber’s hereditary optic neuropathy (LHON). Journal of Medicinal Chemistry 63(22), pp. 13638 -13655. (10.1021/acs.jmedchem.0c00942)
- Cimaglia, G., Votruba, M., Morgan, J. E., André, H. and Williams, P. A. 2020. Potential therapeutic benefit of NAD+ supplementation for glaucoma and age-related macular degeneration. Nutrients 12(9), article number: 2871. (10.3390/nu12092871)
- Bevan, R. J. et al. 2020. OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory. Brain Communications 2(2), article number: fcaa101. (10.1093/braincomms/fcaa101)
- Meschede, I. P., Ovenden, N. C., Seabra, M. C., Futter, C. E., Votruba, M., Cheetham, M. E. and Burgoyne, T. 2020. Symmetric arrangement of mitochondria:plasma membrane contacts between adjacent photoreceptor cells regulated by Opa1. Proceedings of the National Academy of Sciences 117(27), pp. 15684-15693., article number: 3. (10.1073/pnas.2000304117)
- Sun, S., Erchova, I., Sengpiel, F. and Votruba, M. 2020. Opa1 deficiency leads to diminished mitochondrial bioenergetics with compensatory increased mitochondrial motility. Investigative Ophthalmology & Visual Science 61(6), article number: 42. (10.1167/iovs.61.6.42)
- Charif, M. et al. 2020. Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy. Neurology Genetics 6(3), article number: e428. (10.1212/NXG.0000000000000428)
- Varricchio, C., Beirne, K., Heard, C., Newland, B., Rozanowska, M., Brancale, A. and Votruba, M. 2020. The ying and yang of idebenone: Not too little, not too much - cell death in NQO1 deficient cells and the mouse retina. Free Radical Biology and Medicine 152, pp. 551-560. (10.1016/j.freeradbiomed.2019.11.030)
2019
- Jurkute, N. et al. 2019. SSBP1 mutations in dominant optic atrophy with variable retinal degeneration. Annals of Neurology 86(3), pp. 368-383. (10.1002/ana.25550)
- Morny, E. K. A., Patel, K., Votruba, M., Binns, A. and Margrain, T. 2019. The relationship between the photopic negative response and retinal ganglion cell topography. Investigative Ophthalmology & Visual Science 60(6), pp. 1879-1887. (10.1167/iovs.18-25272)
- Jurkute, N. et al. 2019. Clinical utility gene card for: inherited optic neuropathies including next-generation sequencing-based approaches. European Journal of Human Genetics 27, pp. 494-502. (10.1038/s41431-018-0235-y)
- Kousal, B. et al. 2019. Peripapillary microcirculation in Leber hereditary optic neuropathy. Acta Ophthalmologica 97(1), pp. e71-e76. (10.1111/aos.13817)
2018
- Diot, A. et al. 2018. Validating the RedMIT/GFP-LC3 mouse model by studying mitophagy in Autosomal Dominant Optic Atrophy due to the OPA1Q285STOP mutation. Frontiers in Cell and Developmental Biology 6, article number: 103. (10.3389/fcell.2018.00103)
- Dawson, S. R. et al. 2018. Ophthalmology research in the UK's National Health Service: the structure and performance of the NIHR?s Ophthalmology research portfolio. Eye 33, pp. 610-618. (10.1038/s41433-018-0251-8)
2017
- Mahajan, D. and Votruba, M. 2017. Can the retina be used to diagnose and plot the progression of Alzheimer's disease?. Acta Ophthalmologica 95(8), pp. 768-777. (10.1111/aos.13472)
- Carelli, V. et al. 2017. International consensus statement on the clinical and therapeutic management of Leber's Hereditary Optic Neuropathy.. Journal of Neuro-Ophthalmology 37(4), pp. 371-381. (10.1097/WNO.0000000000000570)
- Majander, A. et al. 2017. Childhood-onset Leber hereditary optic neuropathy. British Journal of Ophthalmology 101(11), pp. 1505-1509. (10.1136/bjophthalmol-2016-310072)
- Mahajan, D. and Votruba, M. 2017. A novel NR2E3 gene mutation in autosomal recessive retinitis pigmentosa with cystic maculopathy. Acta Ophthalmologica 95(S259) (10.1111/j.1755-3768.2017.02682)
- Majinder, A. et al. 2017. The pattern of retinal ganglion cell dysfunction in Leber hereditary optic neuropathy. Mitochondrion 36, pp. 138-149. (10.1016/j.mito.2017.07.006)
- Liskova, P. et al. 2017. OPA1 analysis in an international series of probands with bilateral optic atrophy. Acta Ophthalmologica 95(4), pp. 363-369. (10.1111/aos.13285)
- Beirne, K., Rozanowska, M. and Votruba, M. 2017. Photostimulation of mitochondria as a treatment for retinal neurodegeneration. Mitochondrion (10.1016/j.mito.2017.05.002)
- Karaa, A. et al. 2017. Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project. Journal of Inherited Metabolic Disease 40(3), pp. 403-414. (10.1007/s10545-017-0035-5)
- Liao, C. et al. 2017. Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations. Neurology 88(2), pp. 131-142. (10.1212/WNL.0000000000003491)
- Majander, A. et al. 2017. The pattern of retinal ganglion cell loss in OPA1-related autosomal dominant optic atrophy inferred from temporal, spatial, and chromatic sensitivity losses. Investigative Ophthalmology & Visual Science 58(1), pp. 502-516. (10.1167/iovs.16-20309)
2016
- Yu-Wai-Man, P., Votruba, M., Burté, F., La Morgia, C., Barboni, P. and Carelli, V. 2016. A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathologica 132(6), pp. 789-806. (10.1007/s00401-016-1625-2)
- Kushnareva, Y., Seong, Y., Andreyev, A. Y., Kuwana, T., Kiosses, W. B., Votruba, M. and Newmeyer, D. D. 2016. Mitochondrial dysfunction in an Opa1Q285STOP mouse model of dominant optic atrophy results from Opa1 haploinsufficiency. Cell Death and Disease 7, article number: e2309. (10.1038/cddis.2016.160)
- Beirne, K., Rozanowska, M. and Votruba, M. 2016. Red light treatment in an axotomy model of neurodegeneration. Photochemistry and Photobiology 92(4), pp. 624-631. (10.1111/php.12606)
- Navein, A. E. et al. 2016. Disrupted mitochondrial function in the Opa3L122P mouse model for Costeff Syndrome impairs skeletal integrity. Human Molecular Genetics 25(12), pp. 2404-2416. (10.1093/hmg/ddw107)
- Smith, T. G., Seto, S., Ganne, P. and Votruba, M. 2016. A randomized, placebo-controlled trial of the benzoquinone idebenone in a mouse model of OPA1-related dominant optic atrophy reveals a limited therapeutic effect on retinal ganglion cell dendropathy and visual function. Neuroscience 319, pp. 92-106. (10.1016/j.neuroscience.2016.01.042)
2015
- Morny, E. K. A., Margrain, T. H., Binns, A. M. and Votruba, M. 2015. Electrophysiological ON and OFF responses in autosomal dominant optic atrophy. Investigative Ophthalmology & Visual Science 56(13), pp. 7629-7637. (10.1167/iovs.15-17951)
- Pratyusha, G. and Votruba, M. 2015. Retinal changes in a patient with acquired partial lipodystrophy (Laignel-Lavastine and Viard Syndrome). Acta Ophthalmologica 93(7), pp. e598-e599. (10.1111/aos.12690)
- Ganne, P., Garrioch, R. and Votruba, M. 2015. Perceptions and understanding of genetics and genetic eye disease and attitudes to genetic testing and gene therapy in a primary eye care setting. Ophthalmic Genetics 36(1), pp. 50-57. (10.3109/13816810.2014.985845)
- Sergouniotis, P. I. et al. 2015. Clinical and molecular genetic findings in autosomal dominant OPA3-related optic neuropathy. Neurogenetics 16(1), pp. 69-75. (10.1007/s10048-014-0416-y)
2014
- Morris, B. and Votruba, M. 2014. Mean cellular volume in a patient with Leber's optic neuropathy and visual return on alcohol cessation [Letter]. Acta Ophthalmologica 92(1), pp. e77. (10.1111/aos.12100)
- Rowe, F. et al. 2014. The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and results of the research prioritisation survey process. BMJ Open 4(7), article number: e004905. (10.1136/bmjopen-2014-004905)
- Yu-Wai-Man, P., Votruba, M., Moore, A. T. and Chinnery, P. F. 2014. Treatment strategies for inherited optic neuropathies: past, present and future. Eye 28(5), pp. 521-537. (10.1038/eye.2014.37)
2013
- Bailie, M., Votruba, M., Griffiths, P. G., Chinnery, P. F. and Yu-Wai-Man, P. 2013. Visual and psychological morbidity among patients with autosomal dominant optic atrophy [Letter]. Acta Ophthalmologica 91(5), pp. e413-e414. (10.1111/aos.12077)
- Williams, P. A. et al. 2013. Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease. Neurobiology of Aging 34(7), pp. 1799-1806. (10.1016/j.neurobiolaging.2013.01.006)
- Liskova, P. et al. 2013. NovelOPA1missense mutation in a family with optic atrophy and severe widespread neurological disorder. Acta Ophthalmologica 91(3), pp. 225-231. (10.1111/aos.12038)
- Perganta, G. et al. 2013. Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy. PLoS ONE 8(2), article number: e56350. (10.1371/journal.pone.0056350)
- Smith, T. G. and Votruba, M. 2013. Inherited dominant optic neuropathy: from clinical studies to gene function and back again. Drug Discovery Today: Disease Models 10(4), pp. 173-180. (10.1016/j.ddmod.2014.02.001)
2012
- Wells, T. et al. 2012. Opa3, a novel regulator of mitochondrial function, controls thermogenesis and abdominal fat mass in a mouse model for Costeff syndrome. Human Molecular Genetics 21(22), pp. 4836-4844. (10.1093/hmg/dds315)
- Klionsky, D. J., Votruba, M. and and 1268 other authors, . 2012. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8(4), pp. 445-544. (10.4161/auto.19496)
- Liao, C. et al. 2012. Dysregulated mitophagy and mitochondrial transport in severe dominant optic atrophy due to OPA1 mutations [Abstract]. Neuromuscular Disorders 22(S1), pp. S3. (10.1016/S0960-8966(12)70003-2)
- Williams, P. . A., Piechota, M., Von Ruhland, C. J., Taylor, E., Morgan, J. E. and Votruba, M. 2012. Opa1 is essential for retinal ganglion cell synaptic architecture and connectivity. Brain 135(2), pp. 493-505. (10.1093/brain/awr330)
- Morris, B. and Votruba, M. 2012. Leber's optic neuropathy - visual return on alcohol cessation [Letter]. Acta Ophthalmologica 90(7), article number: e568. (10.1111/j.1755-3768.2012.02387.x)
- Chen, L. et al. 2012. OPA1 mutation and late-onset cardiomyopathy: Mitochondrial dysfunction and mtDNA instability. Journal of the American Heart Association, article number: e003012. (10.1161/JAHA.112.003012)
2011
- Powell, K. A., Davies, J. R., Taylor, E., Wride, M. A. and Votruba, M. 2011. Mitochondrial localization and ocular expression of mutant Opa3 in a mouse model of 3-methylglutaconicaciduria type III. Investigative Ophthalmology & Visual Science 52(7), pp. 4369-4380. (10.1167/iovs.10-6406)
- Williams, P. A., Morgan, J. E. and Votruba, M. 2011. Mouse models of dominant optic atrophy: what do they tell us about the pathophysiology of visual loss?. Vision Research 51(2), pp. 229-234. (10.1016/j.visres.2010.08.031)
- Barnard, A. R. et al. 2011. Specific deficits in visual electrophysiology in a mouse model of dominant optic atrophy. Experimental Eye Research 93(5), pp. 771-777. (10.1016/j.exer.2011.07.004)
- Hamblion, E. L., Moore, A. T., Rahi, J. S. and Votruba, M. 2011. Incidence and patterns of detection and management of childhood-onset hereditary retinal disorders in the UK. British Journal of Ophthalmology 96(3), pp. 360-365. (10.1136/bjo.2010.201178)
2010
- Williams, P. A., Morgan, J. E. and Votruba, M. 2010. Opa1 deficiency in a mouse model of dominant optic atrophy leads to retinal ganglion cell dendropathy. Brain 133(10), pp. 2942-2951. (10.1093/brain/awq218)
- Yu-Wai-Man, P. et al. 2010. Multi-system neurological disease is common in patients with OPA1 mutations. Brain 133(3), pp. 771-786. (10.1093/brain/awq007)
- Sheppard, J., Hayes, S., Boote, C., Votruba, M. and Meek, K. M. A. 2010. Changes in corneal collagen architecture during mouse postnatal development. Investigative Ophthalmology & Visual Science 51(6), pp. 2936-2942. (10.1167/iovs.09-4612)
2009
- Yu-Wai-Man, P., Davies, V. J., Piechota, M., Cree, L. M., Votruba, M. and Chinnery, P. F. 2009. Secondary mtDNA defects do not cause optic nerve dysfunction in a mouse model of dominant optic atrophy. Investigative Ophthalmology & Visual Science 50(10), pp. 4561-4566. (10.1167/iovs.09-3634)
- White, K. E., Davies, V. J., Hogan, V. E., Piechota, M., Nichols, P. P., Turnbull, D. M. and Votruba, M. 2009. OPA1 deficiency associated with increased autophagy in retinal ganglion cells in a murine model of dominant optic atrophy. Investigative Ophthalmology & Visual Science 50(6), pp. 2567-2571. (10.1167/iovs.08-2913)
2008
- Davies, V. J. et al. 2008. A missense mutation in the murine Opa3 gene models human Costeff syndrome. Brain 131(2), pp. 368-380. (10.1093/brain/awm333)
2007
- Davies, V. J. et al. 2007. Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. Human Molecular Genetics 16(11), pp. 1307-1318. (10.1093/hmg/ddm079)
- Hayes, S. et al. 2007. Comparative Study of Fibrillar Collagen Arrangement in the Corneas of Primates and Other Mammals. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology 290(12), pp. 1542-1550. (10.1002/ar.20613)
2006
- Davies, V. J. and Votruba, M. 2006. Focus on molecules: the OPA1 protein. Experimental Eye Research 83(5), pp. 1003-1004. (10.1016/j.exer.2005.11.021)
2004
- Aijaz, S., Erskine, L., Jeffery, G., Bhattacharya, S. S. and Votruba, M. 2004. Developmental expression profile of the optic atrophy gene product: OPA1 is not localized exclusively in the mammalian retinal ganglion cell layer. Investigative Ophthalmology and Visual Science 45(6), pp. 1667-1673. (10.1167/iovs.03-1093)
- Votruba, M. 2004. Molecular genetic basis of primary inherited optic neuropathies. Eye 18(11), pp. 1126-1132. (10.1038/sj.eye.6701570)
2003
- Granse, L., Bergstrand, I., Thiselton, D., Ponjavic, V., Heijl, A., Votruba, M. and Andreasson, S. 2003. Electrophysiology and ocular blood flow in a family with dominant optic nerve atrophy and a mutation in the OPA1 gene [Abstract]. Investigative Ophthalmology and Visual Science 44(S), pp. U446.
- Votruba, M., Thiselton, D. and Bhattacharya, S. S. 2003. Optic disc morphology of patients with OPA1 autosomal dominant optic atrophy. British Journal of Ophthalmology 87(1), pp. 48-53.
- Aijaz, S., Bhattacharya, S. S. and Votruba, M. 2003. Expression profile of OPA1, the gene associated with autosomal dominant optic atrophy in the developing and adult mammalian retina [Abstract]. Investigative Ophthalmology and Visual Science 44(E-Abst)
- Votruba, M., Aijaz, S. and Moore, A. T. 2003. A review of primary hereditary optic neuropathies. Journal of Inherited Metabolic Disease 26(2-3), pp. 209-227. (10.1023/A:1024441302074)
2002
- Votruba, M., Hungerford, J., Cornes, P. G. S., Mabey, D. and Luthert, P. 2002. Primary monophasic synovial sarcoma of the conjunctiva [Letter]. British Journal of Ophthalmology 86(12), pp. 1453-1454. (10.1136/bjo.86.12.1453)
- Aung, T. et al. 2002. A major marker for normal tension glaucoma: Association with polymorphisms in the OPA1 gene. Human Genetics 110(1), pp. 52-56. (10.1007/s00439-001-0645-7)
- Thiselton, D. L. et al. 2002. A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 43(6), pp. 1715-1724.
2001
- Thiselton, D. L. et al. 2001. A frameshift mutation in exon 28 of the OPA1 gene explains the high prevalence of dominant optic atrophy in the Danish population: evidence for a founder effect. Human Genetics 109(5), pp. 498-502. (10.1007/s004390100600)
- Votruba, M. 2001. An "overtrained" ophthalmologist responds [Letter]. British Journal of Ophthalmology 85(11), pp. 1394. (10.1136/bjo.85.11.1394)
- Gong, Y. Q. et al. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107(4), pp. 513-523. (10.1016/S0092-8674(01)00571-2)
- Votruba, M. and Gregor, Z. 2001. Neovascular age-related macular degeneration: present and future treatment options. Eye 15(3), pp. 424-429. (10.1038/eye.2001.147)
- Bremner, F. D., Tomlin, E. A., Shallo-Hoffmann, J., Votruba, M. and Smith, S. E. 2001. The pupil in dominant optic atrophy. Investigative Ophthalmology and Visual Science 42(3), pp. 675-678.
- Ocaka, L. et al. 2001. The gene responsibly for autosomal dominant optic atrophy, OPA1 is not associated with normal tension glaucoma [Abstract]. Investigative Ophthalmology and Visual Science 42(4), pp. S564.
2000
- Alexander, C. et al. 2000. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28 [Letter]. Nature Genetics 26(2), pp. 211-215. (10.1038/79944)
- Votruba, M., Leary, S., Losseff, N., Bhattacharya, S. S., Moore, A. T., Miller, D. H. and Moseley, I. F. 2000. MRI of the intraorbital optic nerve in patients with autosomal dominant optic atrophy. Neuroradiology 42(3), pp. 180-183. (10.1007/s002340050041)
1999
- Votruba, M. 1999. Clinical and functional features of patients with dominant optic atrophy - Reply. Archives of Ophthalmology 117(2), pp. 287-288.
1998
- Simunovic, M. P., Votruba, M., Regan, B. C. and Mollon, J. D. 1998. Colour discrimination ellipses in patients with dominant optic atrophy. Vision Research 38(21), pp. 3413-3419. (10.1016/S0042-6989(98)00094-7)
- Votruba, M., Payne, A., Moore, A. T. and Bhattacharya, S. S. 1998. Dominant optic atrophy: exclusion and fine genetic mapping of the candidate gene, HRY. Mammalian Genome 9(10), pp. 784-787. (10.1007/s003359900867)
- Votruba, M., Moore, A. T. and Bhattacharya, S. S. 1998. Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy. Journal of Medical Genetics 35(10), pp. 793-800. (10.1136/jmg.35.10.793)
- Votruba, M., Fitzke, F. W., Holder, G. E., Carter, A., Bhattacharya, S. S. and Moore, A. T. 1998. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Archives of Ophthalmology 116(3), pp. 351-358. (10.1001/pubs.Ophthalmol.-ISSN-0003-9950-116-3-eog7505)
- Votruba, M., Collins, C. M. P. and Harrad, R. A. 1998. The management of solitary trichoepithelioma versus basal cell carcinoma. Eye 12(1), pp. 43-46. (10.1038/eye.1998.7)
- Votruba, M., Moore, A. T. and Bhattacharya, S. S. 1998. Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method - A study of 38 British Isles pedigrees. Human Genetics 102(1), pp. 79-86. (10.1007/s004390050657)
- Holder, G. E., Votruba, M., Carter, A. C., Bhattacharya, S. S., Fitzke, F. W. and Moore, A. T. 1998. Electrophysiological findings in dominant optic atrophy (DOA) linking to the OPA1 locus on chromosome 3q 28-qter. Documenta Ophthalmologica 95(3-4), pp. 217-228. (10.1023/A:1001844021014)
1997
- Votruba, M., Moore, A. T. and Bhattacharya, S. S. 1997. Genetic refinement of dominant optic atrophy (OPA1) locus to within a 2 cM interval of chromosome 3q. Journal of Medical Genetics 34(2), pp. 117-121. (10.1136/jmg.34.2.117)
1994
- Votruba, M. 1994. The case of the disappearing bullet [Letter]. Eye 8(1), pp. 143-144. (10.1038/eye.1994.28)
1993
- Sharma, A. and Votruba, M. 1993. Thymoxamine in the treatment of traumatic mydriasis [Letter]. British Journal of Ophthalmology 77(10), pp. 681. (10.1136/bjo.77.10.681-a)
Addysgu
Undergraduate Optometry Teaching
I lecture to final year Optometry students on the Abnormal Ocular Conditions Course.
Postgraduate Teaching in Ophthalmology
2009
- Neuro-ophthalmology case. Visual recovery in Leber$acirc; s hereditary Optic Neuropathy. Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff
2010
- Practical genetics of optic atrophy. Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff
- Invited Judge for Vision Research Day, Cardiff.
2011
- Retinal ganglion cell dendropathy. Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff.
- Invited Judge for Vision Research Day, Cardiff.
2012
- Mitochondrial eye disease, Ophthalmology Postgraduate Teaching, University Hospital Wales, Cardiff.
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)
INTERNATIONAL INNOVATION - Investigations into genes associated with mitochondrial plasticity; research that will help to inform understanding of eye disease.
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
| 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. $acirc; Morphological assessment of retina in models of hereditary optic neuropathy.$acirc; (Yip WanFen). |
| 2007-2009 | BBSRC Research Grant ( £255,955 over 2 years). J Morgan, W Drexler, M Votruba, M Wride. $acirc; In vitro detection of neuronal programmed cell death by ultrahigh resolution optical coherence tomography.$acirc; |
| 2007 | Wellcome Trust Summer Studentship ( £1400). M Votruba. $acirc; Longitudinal phenotyping in ADOA and new aspects of the phenotype- circadian rhythm and cognitive function.$acirc; (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. $acirc; Histological assessment of tissue from Opa1 mutant mouse.$acirc; £1200 |
| 2012-2013 | Fight for Sight Dr Hans and Mrs Gertrude ~Hirsch Grant Award ( £15,000). M Votruba. $acirc; Find the missing genes: next generation sequencing to accelerate the pace of disease gene discovery in patients with inherited optic neuropathy$acirc; . |
| 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. $acirc; Light therapy for optic neuropathy$acirc; . |
| 2013-2014 | National eye Research Centre. £60,000. M Votruba. "Idebenone in mitochondrial optic neuropathy". |
| 2013-2015 | NIHR Rare Disease Translational Research Collaboration ( £200,000). P Yu-Wai-Man, M Votruba, AT Moore. $acirc; Mitochondrial optic neuropathies$acirc; . |
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$acirc; 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 $acirc; from disease mechanisms to therapeutic strategies. ARVO, May 2012
- Optic neuropathies. For: European Professors of Ophthalmology, Leuven, June 2012
2013
- European Neuromuscular Consortium, Naarden, Holland
Opa1 ocular and CNS effects. Mitochondrial Research Group, John Radcliffe Hospital, Oxford
Research Collaborators:
International
Professor Anne A. Knowlton, M.D., Professor of Medicine and Medical Pharmacology, Molecular & Cellular Cardiology, University of California, Davis, California, USA.
Professor Don Newmeyer, PhD, La Jolla Institute for Allergy and Immunology, La Jolla, CA , USA.
Professor Peter Nuernberg, PhD, Cologne Centre for Genomics, University of Cologne, Germany.
National
Dr Patrick Yu-Wai-Man, MRC Clinician Scientist, Mitochondrial Research Group, The Medical School$acirc; ¨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$acirc; ¨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.
