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Marcela Votruba  BM BCh FRCOphth PhD

Professor Marcela Votruba

BM BCh FRCOphth PhD

Professor and Hon. Consultant in Ophthalmology

School of Optometry and Vision Sciences

Email
VotrubaM@cardiff.ac.uk
Telephone
+44 29208 70117
Campuses
Optometry and Vision Sciences, Room Room 2.30, Maindy Road, Cathays, Cardiff, CF24 4HQ
Main Hospital Building, Room Ophthalmology Clinic, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Comment
Media commentator
Users
Available for postgraduate supervision

Overview

Summary

The Mitochondria & Vision Research Group (M Votruba Lab) is interested in the role of mitochondrial dysfunction due to mutation in an expanding number of genes, in the pathophysiology of inherited optic neuropathy. Our approach has placed an emphasis on generating model systems to study retinal ganglion cell (RGC) loss and inner retinal degeneration. The current direction is to explore and evaluate novel therapeutic interventions.

My research spans two themes- Neuroscience and Ageing (https://www.cardiff.ac.uk/optometry-vision-sciences/research/themes/neurodegeneration-and-ageing)  and Stem cells, Regeneration and Repair (https://www.cardiff.ac.uk/optometry-vision-sciences/research/themes/stem-cells,-regeneration-and-repair).

It is embedded in two multi-disciplinary research groups- Neurodegeneration to Regeneration (https://www.cardiff.ac.uk/research/explore/research-units/n2r) and Ocular Therapeutics (https://www.cardiff.ac.uk/research/explore/research-units/ocular-therapeutics).

As part of my role as a Clinician Scientist, I also manage patients at the University Hospital Wales Eye Department with inherited eye diseases such as inherited retinal dystrophies and optic neuropathies, running a Retinal Clinic and a Genetic Eye Clinic. I also take part in both commercial and academic clinical research and trials. I am the HCRW National Ophthalmology Specialty Lead for Wales & Member of the UK NIHR Specialty Lead Panel for Ophthalmology.

Previously I served as Head of the School of Optometry & Vision Sciences for 6 years) (2014-2019).

Research Overview

My goals are aimed at developing a deeper understanding of inherited eye disease and ultimately utilizing 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 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 characterize the disease phenotype and clone the disease gene, my group has analyzed 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 and exploring and testing novel therapies.

https://www.youtube.com/watch?v=PjP8ACbprKc

See most recent LHON Forum 2022 recording:  www.opticnervenetwork.com

https://faculti.net/visual-improvement-in-patients-with-lebers-hereditary-optic-neuropathy/

HCRW Specialty Lead Ophthalmology: https://healthandcareresearchwales.org/votruba

https://www.fightforsight.org.uk/news-and-articles/articles/news/international-womens-day-2023/

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Research Interests

My research focus is on the role of mitochondria 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 utilising retinal ganglion cell lines and primary RGCs, to explore the effect of mitochondrial fusion and fission genes on cell viability and the mechanism of cell death. We are also exploring the role of neuroprotective agents. OPA1 is known to bind to the 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.

Current clinical trial recruitment

A prospective natural history study of patients with autosomal dominant optic atrophy (FALCON). Sponsor Stoke Therpaeutics STK-001

An Open-label Study to Investigate the Safety, Tolerability, and Exposure of Single Ascending Doses of the Antisense Oligonucleotide STK-002 in Patients with Autosomal Dominant Optic Atrophy (OSPREY). Sponsor Stoke Therpaeutics STK-002 Phase 1 ADOA

Global Patient Registry of Inherited Retinal Diseases EYE-RD Registry. Sponsor Janssen Research & Development LLC

For all patient trial recruitment please contact votrubam@cf.ac.uk or hayley.westwood@wales.nhs.uk

Current Postgraduate Research Students

2021-2024 Mariia Grudina, Primary supervisor Marcela Votruba. Co-supervisors Ben Mead & Malgorzata Rozanowska. Title: "Human induced pluripotent stem cell models for the study and treatment of mitochondrial optic neuropathies".

2021-2024 Turkish Scholarship. Esmahan Durmez, co-supervisor with Ben Mead. Title: "Therapeutic testing of exosomes for retinal disease".

2022-2025 International Glaucoma Association Studentship. Matyas Kutnyanszky. Title: "Exosomes for glaucoma therapeutics".

Research Alumni

Post- doctoral Research Associates

  • Dr Vanessa Davies
  • Dr Ruby Grewel
  • Dr Andrew Hollins
  • Dr Kate Powell
  • Dr Terry Smith
  • Dr Kathy Beirne
  • Dr Carmine Varrachio
  • Dr Irina Erchova
  • Dr Dinesh Kumar Kandaswamy, Newton International Fellow
  • Dr Matthieu Trigano
  • Dr Thomas Freeman
  • Dr Gloria Cimaglia
  • Dr Wyn Firth

Technical Assistants

  • Elaine Taylor
  • Sharon Seto
  • Pascale Aeschlimann

Former PhD Students

  • Dr Jack Sheppard
  • Dr Gosia Piechota
  • Dr Jennifer Davies
  • Professor Pete Williams
  • Dr Carolyn Walker
  • Dr Kathy Beirne
  • Dr Carmine Varricchio
  • Dr Shanshan Sun
  • Dr Gloria Cimaglia

Professional Training Scheme

  • Rebecca Thirgood

EVER Foundation Fellows

  • Dr Pratyusha Ganne BM BCh FRCOphth
  • Dr Deepti Mahajan  MD FRCOphth

Summer Students

Dr Marrios Sarros MD, Dr Costas Karabatsas MD, Yip Wan Fen NSc, Laura Byrne, Amanda Mui, Rebecca Watts, Roshini Joseph, Oliver Coppleston, Christopher Man, Kestutis Satkus

Recent & current grant funding

2024-2025              BMA Dawkins & Strutt Research Grant. Votruba M. "Mitochondrial transfer in optic neuropathy".

2023-2026              Fight for Sight Project Grant. Votruba M, Morgan J, Mead B, Rozanowska M. "RGC structure and mitochondrial function in LHON: the paradox of recovery and an extended therapeutic window.”

2019-2022                Academy of Medical Sciences Newton International Fellowship. Host  M Votruba. Fellow  Dinesh Kumar Kandaswamy. “Near-infrared light therapy as a therapeutic regimen for inherited optic neuropathy.”

2019-2022                   Fight for Sight Studentship. Morgan JE, Votruba M, Williams P. “NAD therapy in glaucoma”.

2020-2022                  National Eye Research Centre Project Grant. “Sustained release formulations for new drugs in the treatment of mitochondrial optic neuropathies.”  Votruba M, Brancale A, Rozanowska M and Heard C.

2019-2020                  Wellcome Trust ISSF3 Consolidator Award. C Varrachio. M Votruba, Sponsor B Newlands.

2019-2020                  Wellcome Trust ISSF3 Cross-Disciplinary Award. Light for Sight – neuroprotection in mitochondrial optic neuropathy. M Votruba, M Rozanowska, J Hicks, S Armstrong.

 

Research Collaborators

International

Professor Pete Williams, Assistant Professor, Dept. of Clinical Neuroscience, Section of Ophthalmology and Vision, Karolinska Institute, Stockholm

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

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

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

Professor Sayan Roy, Ph.D., FARVO, Professor of Medicine, Section of Diabetes, Endocrinology & Nutrition  & Professor of Ophthalmology, Boston University School of Medicine, USA.

National

Professor Patrick Yu-Wai-Man, MRC Clinician Scientist, Mitochondrial Research Group, The University of Cambridge and UCL, Moorfields Eye Hospital

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

Professor Jo Poulton, Ph.D. MRCP, Professor of Mitochondrial Genetics, John Radcliffe Hospital, University of Oxford

Professor Tim Wells, Ph.D., School of Bioscience, Cardiff University.

Dr Ben Newland  Ph.D., Welsh School of Pharmacy and Pharmaceutical Sciences, Cardiff University

Teaching

Undergraduate and Postgraduate Optometry Teaching

I lecture and examine final-year optometry students on abnormal ocular conditions, and final-year research projects.

I supervise MSc projects for optometrists.

Postgraduate Teaching in Ophthalmology

I participate in postgraduate teaching in ophthalmology at the University Hospital, Wales.

Biography

I am a clinically qualified and clinically active Professor of Ophthalmology at Cardiff University School of Optometry & Vision Sciences and an Honorary Consultant Ophthalmologist at the University Hospital of Wales, Cardiff. Since 2020 I have been Visiting Researcher, at Karolinska Institutet, Stockholm, and since 2019 Visiting Professor at Charles University, Prague, Czech Republic, and an Honorary member of the Scientific Board of the First Faculty of Medicine, Charles University, Prague.

I was awarded a Personal Chair at Cardiff University in 2011, having been Senior Lecturer there since 2003. I came to Cardiff from UCL with a Clinician Scientist Fellowship from the MRC, with personal funding and funding for a research associate for four years.  Prior to this, I was a Consultant in Medical Retina, at Moorfields Eye Hospital, London, UK in 2003 and a Visiting Researcher, at the National Eye Institute, National Institutes of Health, USA, in 2002. I was a fellow to Professor Paul Sieving, in 2002- first in Michigan, Ann Arbor at the Kellogg Eye Centre, and then at the National Eye Institute, National Institutes of Health, Bethesda. I completed my specialty and supra-specialty training in ophthalmology and ophthalmic genetics in 2000 and was awarded my certificate of completion of training. I was a clinical fellow under the guidance of Professors Tony Moore and Alan Bird and trained in medical retina and genetics at a world-leading center. My fellowship of the Royal College of Ophthalmology (FRCOphth) was awarded in 1992. I studied Physiological Sciences at The Queen’s College, Oxford (BA, MA Hons 2:1, 1984/ 1987), where I was awarded an Open Scholarship in 1981. My Medical degree was at Green College, Oxford (BM BCh, 1987).

Honours and awards

Distinguished Fellowships

2017 Elected Fellow of the Learned Society of Wales

2019 Visiting Professor at Charles University, Prague, Czech Republic

2023 Honorary member of the Scientific Board of the First Faculty of Medicine, Charles University, Prague, Czech Republic.

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

Postgraduate Prizes

1996                                  The Royal Society of Medicine: Ophthalmology Section-Registrars’ Meeting: First Prize (Awarded for the Best Paper at Annual Training Meeting)

Undergraduate Distinctions

1981                                   Open Scholarship, The Queen’s College, Oxford

1984                                   First Class Hons. Dissertation, Oxford University

1987                                   Final Year Clinical Prize: Green College, Green College, Oxford

Professional memberships

Memberships, Affiliations and Societies

European Vision Institute (EVI)

European Paediatric Ophthalmology Society (EPOS)

British Eye Study Group (BESG)

UK Eye Genetics Group (UK EGG)

European Retina, Macula and Vitreous Society (EuroRetina)

Association for Research in Vision & Ophthalmology (ARV0)

International Society of Eye Research (ISER)

European Association for Vision & Eye Research (EVER)

European Society Human Genetics (ESHG)

The Oxford Ophthalmological Congress (OOC)

International Society for Genetic Eye Disease (ISGED)

Academic positions

Present Substantive Appointment

Professor of Ophthalmology, Cardiff University  and Consultant in Ophthalmology, Cardiff & Vale NHS Trust, University Hospital Wales

Previous Substantive Appointments

Jan 2014- Dec 2019                 Head of School of Optometry & Vision Sciences, Cardiff University

Aug 2011 - Dec 2013                Professor and Honorary Consultant in Ophthalmology, Cardiff University and The Cardiff & Vale    NHS Trust, University Hospital of Wales

Oct 2007  - July 2011                Honorary Consultant Senior Lecturer, Cardiff University and The Cardiff & Vale NHS Trust, University Hospital of Wales.

Oct 2003 - Sep 2007                  MRC Clinician Scientist Fellow & Honorary Consultant Senior Lecturer, Cardiff University and The University Hospital of Wales

Apr 2003 - Oct 2003                   Consultant in Medical Retina, Moorfields Eye Hospital, London & Service Lead for Audit & Clinical Governance & Service Lead for ARMD Research

Other Appointments

2019 -ongoing                          Visiting Professor, Charles University Prague, Czech Republic

2002                                         Visiting Research Scholar, National Eye Institute, National Institutes of Health, Bethesda, MD, USA

Committees and reviewing

Grant advisory panels

  • 2020-2023  Deputy Chair, Fight for Sight Grant Advisory Panel, UK
  • 2015 – 2020 Member Grant Advisor Panel, National Eye Research Centre, UK
  • 2017– 2022 Member Grant Advisory Board, RP Fighting Blindness/ Retina UK
  • 2012 – 2017 Member Grant Advisory Panel, Fight for Sight, UK

Leadership roles in learned societies or professional bodies

  • 2019-2023 Secretary General, European Association for Vision and Eye Research.
  • 2019-2023 Representative for European Association for Vision & Eye Research on EU-EYE Board and on the EVERfoundation Board, and on the TRANSFORM Alliance.
  • 2018- 2020 Invited Member of the James Lind Alliance Priority Setting Partnership Steering Board: “Rare Mitochondrial Diseases”.
  • 2016 - 2018 National Ophthalmology Specialty Lead for Wales.
  • 2016 - 2018 Member of the UK Specialty Lead Panel for Ophthalmology Trials.
  • 2014 - 2017 Member of the VISION 2020 UK Eye Research Committee.
  • 2012- 2014 Lead Principal Investigator and Co-ordinator of the MRC Mouse Eyes & Vision Consortium.
  • 2012 - 2017 Member Steering Committee, UK Eye Genetics Group.
  • 2012 - 2013 Royal College of Ophthalmologists Representative on James Lind Alliance Priority Setting Partnership Steering Committee: “Sight Loss and Vision”.
  • 2013   Invited Faculty Member, European Neuromuscular Consortium, Naarden, Holland.
  • 2011 - 2016 Programme Secretary, European Association for Vision and Eye Research.
  • 2009 - 2010 Vice President, European Association for Vision and Eye Research.
  • 2004 - 2009 Section Chair for Molecular Biology/ Genetics/ Epidemiology, Board of European Association for Vision and Eye Research (EVER).

Editorships of journals

  • 2013- present: Associate Editor, Editorial Board of Acta Ophthalmologica,
  • 2020- present: Associate Editor Therapeutic Advances in Rare Disease

Guest editorships of books or special editions of journals

  • 2013 Guest Editor for Drug Discovery Today: Disease Models

Other examples of leadership in the academic community

  • 2008 & 2011 Jury member, Belgian Ophthalmology Research Prize.
  • 2004 & 2009 Jury member, College of Ophthalmologists Research Prize.

Leadership roles in industry

  • Expert Panel Member, Novartis Gene Therapy for RPE65 Leber’s congential amaurosis, London 2018
  • Expert Panel Member, Chair and Invited Speaker at Mitochonrial optic neuropathies“, Santhera Pharmaceuticals, Prague, 2019

Review of papers for scientific journals

I regularly review papers for scientific journals, including ophthalmology and neuroscience journals- Brain, Investigative Ophthalmology & Vision Science, Archives of Ophthalmology, The British Journal of Ophthalmology, Eye, Ophthalmic Research, Neuro-ophthalmology, Acta Ophthalmologica and Experimental Eye Research and genetics journals- Human Molecular Genetics, American Journal of Human Genetics, Journal of Medical Genetics, Human Genetics, European Journal of Human Genetics and Ophthalmic Genetics.

I also regularly review Grant Applications for national bodies- The MRC, The Wellcome Trust, Fight for Sight, The Macular Disease Society, The Guide Dogs for the Blind Association, The Iris Fund, the National Eye Research Center and international bodies, including, the Swiss National Science Foundation and Association Francaise contre les Myopathies.

Supervisions

Current students

2019-2023

Fight for Sight Studentship Gloria Cimaglia, co-supervisor with James Morgan and Pete Williams. Title: “NAD in glaucoma neuroprotection”.

2021-2024

Mariia Grudina, Primary supervisor Marcela Votruba. Co-supervisors Ben Mead & Malgorzata Rozanowska. Title: "Human induced pluripotent stem cell models for the study and treatment of mitochondrial optic neuropathies".

2021-2024

Turkish Scholarship. Esmahan Durmez, co-supervisor with Ben Mead. Title: ""Therapeutic testing of exosomes for retinal disease".

I am interested in supervising PhD students in the areas of:

  • Role of mitochondria in neurodegeneration
  • Novel therapies for mitochondrial optic neuropathies
  • iPS cells for the testing of novel therapy of mitochondrial dysfunction
  • Mitochondrial damage in age related macular degeneration
  • Quality of life in patients with inherited retinal and optic nerve disease, utility of novel therapies

Current supervision

Mariia Grudina

Mariia Grudina

Research student

Esmahan Durmaz

Esmahan Durmaz

Research student

Matyas Kutnyanszky

Matyas Kutnyanszky

Research student