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About
Professor Keith Martin
CERA Managing Director, Head of Glaucoma Research
Professor Keith Martin is CERA’s Managing Director. His research focus is on glaucoma, particularly investigating new strategies to protect and regenerate the optic nerve.
Professor Keith Martin
CERA Managing Director, Head of Glaucoma Research
MA BM BCh DM MRCP FRCOphth, FRANZCO FARVO FAAPPO ALCM
Professor Keith Martin is a clinician scientist ophthalmologist and Ringland Anderson Professor and Head of Ophthalmology at the University of Melbourne.
He was previously Professor and Head of Ophthalmology and Deputy Director of the Centre for Brain Repair at the University of Cambridge.
His research is focused on developing new strategies to protect and regenerate the optic nerve in glaucoma, the leading cause of irreversible blindness worldwide. He was first in the world to demonstrate gene therapy and stem cell therapy could reduce retinal ganglion cell death in an experimental model of glaucoma.
A gene therapy for glaucoma developed in his lab is currently being progressed towards human clinical trials by a major pharmaceutical company. He has extensive experience in optic nerve injury models, including multiple animal models of glaucoma, retinal gene therapy and all relevant surgical techniques.
Professor Martin is co-founder of Quethera, a Cambridge-based gene therapy company which developed a gene therapy for glaucoma that is currently in advanced pre-clinical development, and Ikarovec, a second gene therapy spin out company from his Cambridge lab developing gene therapies for common retinal diseases.
He is also a founding Director of three further spin out companies from the Centre for Eye Research Australia: Mirugen, developing cell reprogramming technology for inherited retinal diseases; Enlighten Imaging, developing hyperspectral imaging technology for the diagnosis of retinal and neurological diseases; and Cerulea Clinical Trials, a new state-of-the-art ophthalmic clinical trials facility that recently received a $10m investment from the Victorian Government.
Clinically, Professor Martin specialises in the medical and surgical management of complex glaucoma. He was President of the World Glaucoma Association from 2018-20, is a Past President of the UK and Ireland Glaucoma Society and is currently Chair of the Australia and New Zealand Glaucoma Society.
He is an experienced supervisor and mentor to graduate students, post docs and clinician scientists. Clinically, he specialises in the medical and surgical management of advanced glaucoma.
Key research questions
- Can gene therapy be used to treat patients with glaucoma whose vision is deteriorating despite conventional treatment to lower the eye pressure?
- Can we regenerate the damaged optic nerve to achieve useful restoration of vision?
- Can Vitamin B3 supplementation protect or improve visual function in glaucoma patients?
- Can high resolution imaging of aqueous outflow (Haemoglobin Video Imaging) help improve the efficacy of glaucoma surgery?
- Can we design, engineer and test in clinical trials new devices that help preserve the vision of glaucoma patients more effectively than existing technology?
- Can we find new biomarkers that can shorten glaucoma clinical trials and improve patient care by helping us predict those most at risk of progressive visual loss?
- Can we protect and repair the mechanisms by which retinal ganglion cells regulate their own blood flow in glaucoma?
- Can we reprogram other cells in the retina to replace retinal ganglion cells lost in glaucoma?
Current projects
Selected publications
My team
Key collaborators
Funding and support
Current projects
Gene therapy for glaucoma
Up to 1 in 8 patients with glaucoma go blind in at least one eye during their lifetime despite currently available treatments. We have developed a gene therapy that has been shown to protect vision in experimental models of glaucoma. We are currently working with Astellas Inc to progress this therapy towards human clinical trials.
Promoting retinal ganglion cell survival and optic nerve regeneration by enhancing transport of growth and survival receptors
We are using techniques that modulate axonal transport to protect retinal ganglion cells from the glaucomatous injury, and to stimulate orderly regrowth of injured axons. Integrins are molecules that can steer regeneration, however integrins are not efficiently transported in the optic nerve. We found that if we manipulate integrin transport into axons then other beneficial molecules come too, making the axon better at regenerating. We are pursuing this work together with international collaborators in Cambridge and London.
The effect of Vitamin B3 supplementation on visual function in glaucoma
In a recent randomised clinical trial led by Professor Jonathan Crowston and Dr Flora Hui, 12 weeks of high-dose Vitamin B3 supplementation led to significant improvement in retinal function in patients with glaucoma. We are currently leading a group of coordinated international clinical trials in Australia, Singapore, Sweden and the UK that will determine if vitamin B3 supplementation can reduce visual loss in glaucoma over 2 years. Together, these trials will recruit over 1,000 patients internationally, representing one of the largest ever studies of a potential neuroprotective therapy for glaucoma.
Enhancing blood supply via tunneling nanotubes to prevent neurodegeneration and vision loss in glaucoma
In collaboration with Luis Alarcon-Martinez at CERA, we are investigating how retinal ganglion cells (the nerve cells that make up the optic nerve) talk to blood vessels to regulate their blood supply in health and disease. We are exploring how this communication is damaged in glaucoma, and how it can be protected and repaired in the future.
Selected publications
Development of the first gene therapy for glaucoma:
1. Martin KR, Quigley HA, Zack DJ, Klein RL, Levkovitch-Verbin H, Valenta D, Baumrind LA, Pease ME, Hauswirth WW. Gene therapy with brain derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE 2003;43:2236-2243. DOI: 10.1167/iovs.02-1332
First in the world to demonstrate gene therapy could protect against optic nerve damage in experimental glaucoma.
2. Osborne A, Khatib TZ, Songra L, Barber AC, Hall K, Kong GYX, Widdowson PS, MARTIN KR. Neuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signaling. CELL DEATH AND DISEASE. 2018 Sep 26;9(10):1007. DOI: 10.1038/s41419-018-1041-8
World first demonstration of sustained optic nerve protection in experimental glaucoma by a novel gene therapy that protects retinal ganglion cells. The therapy was effective in reducing optic nerve damage in multiple injury models in multiple species with multiple different structural and functional endpoints. This gene therapy is currently progressing towards human clinical trials in partnership with a major pharmaceutical company. For the work described in this paper we were Runner Up in the UK Government’s BioStart Synthetic Biology Competition 2017
3. Khatib TZ, Osborne A, Yang S, Ali Z, Jia W, Manyakin I, Hall K, Watt R, Widdowson PS, MARTIN KR. Receptor-ligand supplementation via a self-cleaving 2A peptide–based gene therapy promotes CNS axonal transport with functional recovery. SCIENCE ADVANCES. 2021 Mar 31;7(14):eabd2590. DOI: 10.1126/sciadv.abd2590
First demonstration that modulation of BDNF signalling with gene therapy can protect visual function in experimental glaucoma
Development of the stem cell therapy for glaucoma:
4. Johnson TV, DeKorver NW, Levasseur V, Osborne A, Tassoni A, Lorber B, Heller JP, Villasmil R, Bull ND, MARTIN KR*, Tomarev SI*. Identification of retinal ganglion cell neuroprotection conferred by platelet-derived growth factor through analysis of the mesenchymal stem cell secretome. BRAIN. 2014 Feb;137(Pt 2):503-19. DOI: 10.1093/brain/awt292 *Joint senior and corresponding authors
We were first in world to demonstrate optic nerve protection by stem cell transplantation in experimental glaucoma. In this paper, we identified the mechanism of this neuroprotection as related to production of PDGF by transplanted cells
5. Osborne A, Sanderson J, MARTIN KR. Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived Growth Factor on Human Retinal Ganglion Cells. STEM CELLS. 2018 Jan;36(1):65-78. DOI: 10.1002/stem.2722
First in the world to show human mesenchymal stem cells could protect human retinal ganglion cells under organ culture conditions.
Key clinical trials:
6. Garway-Heath DF, Crabb DP, Bunce C, Lascaratos G, Amalfitano F, Anand N, Azuara-Blanco A, Bourne RR, Broadway DC, Cunliffe IA, Diamond JP, Fraser SG, Ho TA, MARTIN KR, …, Zeyen TG. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. THE LANCET. 2015 Apr 4;385(9975):1295-304. DOI: 10.1016/S0140-6736(14)62111-5
Landmark clinical study published in the Lancet; Demonstrates my contribution to the first placebo-controlled trial to show visual field preservation through lowering of intraocular pressure with topical drugs in patients with OAG, and the first to show the visual field–preserving effect of a topical prostaglandin analogue
7. Medeiros FA, MARTIN KR, Peace J, Scassellati Sforzolini B, Vittitow JL, Weinreb RN. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: the LUNAR Study. AMERICAN JOURNAL OF OPHTHALMOLOGY 2016 Aug;168:250-9. DOI: 10.1016/j.ajo.2016.05.012
8. Hui F, Tang J, Williams PA, McGuinness MB, Hadoux X, Casson RJ, Coote M, Trounce IA, MARTIN KR, van Wijngaarden P, Crowston JG. Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial. CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY. 2020 Sep;48(7):903-914. DOI: 10.1111/ceo.13818
The landmark first human clinical study to demonstrate that vitamin B3 supplementation could improve visual function in some patients with glaucoma.
Other work:
9. Lorber B, Hsiao WK, Hutchings IM, MARTIN KR. Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing. BIOFABRICATION. 2014 Mar;6(1):015001. DOI: 10.1088/1758-5082/6/1/015001
World first demonstration that retinal ganglion cells can be inkjet printed.
10. Petrova V, Pearson CS, Ching J, Tribble JR, Solano AG, Yang Y, Love FM, Watt RJ, Osborne A, Reid E, Williams PA, MARTIN KR, Geller HM, Eva R, Fawcett JW. Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS. NATURE COMMUNICATIONS 2020 Nov 5;11(1):5614. DOI: 10.1038/s41467-020-19436-y
First demonstration of optic nerve regeneration achieved by overexpression of protrudin.
My team
- Dr Flora Hui – Post Doctoral Researcher, CERA
- Dr Andrew Osborne – Post Doctoral Researcher, University of Cambridge
- Fiona Love – PhD student, University of Cambridge
- Thomas Jacobs (Leuven) – PhD student, University of Melbourne
- Jesse Gardner-Russell – PhD student, University of Melbourne
- Mahmoud Haddara – PhD student, University of Melbourne
- Yan Zhang – PhD student (Committee Chair), University of Melbourne
Key collaborators
CERA:
- Dr Raymond Wong – Head of Cellular Reprogramming Research
- Dr Luis Alarcon-Martinez – Head of Visual Neurovascular Research
- Dr Jennifer Fan Gaskin – Head of Ocular Fibrosis Research
- Associate Professor Guei-Sheung (Rick) Liu – Head of Genetic Engineering Research
- Dr Nathan Kerr – Principal Investigator, Glaucoma Surgical Research
- Professor Michael Coote – Principal Investigator, Glaucoma Surgical Research
University of Cambridge:
King’s College, London
Karolinska Institute, Stockholm:
University of Sydney:
Moorfields / University College, London
Funding and support
Thank you to the following organisations for their support:
- Fight for Sight
- Medical Research Council
- Cambridge Eye Trust
- Jean Miller Foundation
- Connie and Craig Kimberley Fund
- Fighting Blindness Canada
Contact Professor Keith Martin
keith.martin@unimelb.edu.au
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