Robert MacLaren was born on 14 November 1966, at Epsom in Surrey.[5] His father was a photographer, which prompted an early interest in optics. MacLaren was educated and trained at the University of Edinburgh Medical School, from 1985 to 1990, where he graduated with a Bachelor of Medicine and a Bachelor of Surgery. MacLaren then earned an academic doctorate, between 1992 and 1995, at the University of Oxford. The doctorate was for his work on optic-nerve regeneration.[citation needed]
Ophthalmology
MacLaren was appointed Professor of Ophthalmology at the University of Oxford in March 2009.[1] In February of the same year, he was made Honorary Professor of Ophthalmology at the UCL Institute of Ophthalmology. He has been a Fellow of the Royal College of Ophthalmologists (FRCOphth) since June 2003.
MacLaren is described as 'one of the stars' of the developing inter-disciplinary field of ophthalmic translational medicine (TM). This combines practical skills in eye surgery with clinical academic application in research, to investigate the diseases of the eye 'from bench to bedside': aiming to improve patient outcomes, at least by arresting or slowing the progress of a disease, or – ideally – by reversing the effects, partially or totally. Once the processes of the diseases are understood, new surgical technologies are furthering the options for a surgical solution and new ophthalmic technologies have created a variety of implants, such as electronic retinal devices for prosthesis. Furthermore, the enhanced precision of surgery allows additional interventions, with the application of gene therapy and stem-cell therapy to retinal dystrophies (inherited conditions).[7]
Surgery
Horizontal section of right eye, looking upwards. The retina and macula are at the back of the eye
He has been a Fellow of the Royal College of Surgeons of Edinburgh (RCSEd) since July 1998 and was awarded their annual King James IV Professorship in 2007.
MacLaren was the assistant surgeon to James Bainbridge and helped perform the world's first retinal gene therapy treatment. The operation was carried out at Moorfields in London. The patient was Robert Johnson, a young man with Leber's Congenital Amaurosis (LCA). A faulty gene in the pigment layer, RPE65, prevented his photoreceptor cells from working, so a valid copy of the gene was implanted in one eye to 'patch' the blind-spot and restore function.[9] The delicate operation required passing a needle through the eye, to lift the retina and insert the new gene-copy in the pigment layer.
2011 Choroideremia Gene Therapy Trial
This trial was funded by the Health Innovation Challenge Fund[10] and the Oxford (OUH) BRC. It addressed the progress of the disease choroideremia, or choroideraemia, in which a faulty gene, CHM, leads to a loss of REP1 protein, affecting the retinal pigment epithelium (RPE) and causing progressive loss of vision. On 24 November 2011, Jonathan Wyatt, a Bristol barrister, received a 'good copy' of the REP1 gene, administered through an adeno-associated virus (AAV) – serotype 2 (AAV2) – as a vector, in fluid under the retina. By 2016, the results of the trial appeared both 'promising and lasting' and further work was authorised, with a view to seeing whether the process could eventually be applied to more common conditions, such as age-related macular degeneration (AMD).
2012/2015 Electronic Retinal Implant Trials
These trials, funded by the NIHR and the Oxford (OUH) BRC, tested the ability of an electronic retina to replace a retina that has become damaged, a development common in patients with the hereditary condition retinitis pigmentosa (RP). The implants were developed by German company Retina Implant AG.[11] The devices also require a power-plant to be inserted behind the ear, in the manner of a cochlear implant.
The pilot-trial of 22 March 2012 tested the Alpha IMS device. The supporting power-plant procedure was carried out by surgeon James Ramsden with Markus Groppe. The main operation was undertaken, at Oxford, by MacLaren with Tim Jackson, consultant surgeon at Kings College Hospital.[12] The patient was Chris James, a council-worker from Wiltshire. MacLaren suggested that if the trial were successful, an electronic retina could become standard for patients with retinitis pigmentosa (RP). He warned that current devices were not suitable to treat age-related macular degeneration (AMD) or diseases of the optic-nerve, such as glaucoma.[13] The following week, Jackson, with MacLaren, operated on Robin Millar, a music-producer, in London; another four UK patients also received the device during that year.
On 8 June 2015, the improved Alpha AMS device was implanted in the first patient, again with MacLaren carrying out the procedure, in Oxford.[14]
2016 Robot-Assisted Surgery Trial
In the past, retinal diseases of the eye could be monitored to microscopic level – using laser scanners and microscopes – but interventions were not possible because the delicate nature of the eye meant that surgical operations were beyond the physiological limits of the human hand. On 9 September 2016, operating at the John Radcliffe Hospital in Oxford, MacLaren and Thomas Edwards[15] performed the world's first robot-assisted operation inside the eye. The patient was William Beaver, a local priest.
This operation was described as the 'R2D2 Trial', because it was testing the safety and efficacy of the Robotic Retinal-Dissection Device (R2D2), developed by Dutch firm Preceyes BV (pronounced: precise!).[16] The operation involved lifting off a damaged membrane, 100th millimetre thick, from the retina, at the back of the eye; the robot's tolerance, however, would have allowed work to 1000th millimetre.[17] The operation proved the efficacy of the new technologies available, allowing the possibility of exploiting their potential to new scientific and a medical ends: MacLaren said that with robotic systems, a whole new chapter of eye surgery had just begun.
Mutations in the X-linked RPGR gene are the most common cause of severe sight loss in retinitis pigmentosa. The RPGR gene contains a highly repetitive sequence of purine bases in the DNA with a large section comprising almost exclusively Guanine or Adeninenucleotides, which made it very difficult to clone it for gene therapy. Using a form of gene editing known as codon-optimisation, MacLaren and members of his research team were able to engineer a stable version of RPGR that was expressed highly efficiently in an AAV vector.[18] This led to the first gene therapy trial for X-linked retinitis pigmentosa sponsored by Nightstar and with MacLaren as the surgeon.[19]
Research
The Oxford NIHR Biomedical Research Centre (OxBRC)[20] is, as evidenced by NIHR funding allocation, one of England and the UK's leading centres for medical research. It is sometimes styled 'Oxford (OUH) NIHR BRC' since the establishment of a second BRC in Oxford: the Oxford Health NIHR BRC. The OxBRC's NHS Host is the Oxford University Hospitals NHS Trust, where MacLaren is a Consultant Ophthalmologist and its Academic Partner is the University of Oxford, where MacLaren is also Professor of Ophthalmology. Additionally, in 2016, the NIHR appointed MacLaren to be a senior investigator, or lead researcher, for the speciality of ophthalmology.[2]
His current clinical and laboratory research efforts focus on the forms of blindness which are to date incurable. By understanding the causes of retinal degeneration, it may be possible to slow, arrest or ameliorate the processes. The ultimate aim is then to reverse such effects and to restore working vision.[7] The research efforts concentrate on two areas of the eye in particular: the retinal pigment epithelium (RPE), and the photoreceptors. The NLO Clinical Ophthalmology Research Group ('the MacLaren Group')[22] is looking at replacement methods for each, and for both, to improve patient outcomes.[7] Electronic retinal implants have already been trialled to treat retinitis pigmentosa, and trials are now being conducted to treat choroideremia through gene-therapy: implanting missing or faulty genes to correct retinal dystrophies (inherited conditions).
As well as retinal issues, research is undertaken to improve outcomes for conditions relating to the lens and to the optic nerve, such as improved intra-ocular lenses (IOL) for cataract operations and therapies for glaucoma.
Teaching
Oxford University DPhil, in full academicals.
In addition to his other duties, MacLaren has a full programme of teaching and tutoring. He is formally qualified, with a Postgraduate Diploma in Learning and Teaching in Higher Education (PGDipLATHE) from 2006.[23] He has been a Fellow of the Higher Education Academy since June 2003.
As a Bodley Fellow – the active staff of the college – at Merton, since October 2007, he is a stipendiary lecturer in human anatomy.[24] He has held weekly tutorials in medical sciences for undergraduates since 1992: anatomy, genetics and cell biology for Year 1, and neuroanatomy and visual neuroscience for year 2; third year FHS topics relate to gene therapy, stem cells or visual neuroscience.
As a mentor at the Academy of Medical Sciences, he supervises clinical academics. He also supervises junior doctors training in ophthalmic surgery and DPhil research students.[4]
Business
In 2014, with Oxford University, he co-founded the private bio-technology company NightstaRx Ltd.,[25] also known Nightstar, in which he remains a director, and which is based at the offices of the Wellcome Trust in London.
The technology spin-out was developed with Oxford Innovation, Ltd. and Syncona Ltd. and the clinical-stage company now is backed by Syncona, NEA venture capital and Oxford Science Equity-Management (OSEM).[26][27] The company has received four rounds of funding, including its IPO on NASDAQ in September 2017.[28][29][30]
MacLaren was posted to the Honourable Artillery Company (HAC) and, in due course, became the Surgeon-Major: the Regimental Medical Officer (RMO). The term Surgeon-Major applied to all the unit's RMOs, most of whom were in General Practice (GP), and it was coincidental that Major MacLaren was primarily an occupational surgeon. Major MacLaren also served as locum RMO to the Household Cavalry Mounted Regiment, at Knightsbridge in London.[21]
In addition to serving as an RMO, Major MacLaren volunteered for an operational tour, in the former Yugoslavia, engaged in the field of military medicine, as part of 1st Mechanised Brigade,[21] with case-work based more on occupational injury and trauma medicine, rather than disease and genetics.
Robert MacLaren is married with three children: two boys and a girl.[33] He is the grandson of the lawyer Robert Edwin NewberyMC, great-great grandson of the Victorian actor/playwright James Roland MacLaren and great-great-great grandson of the engineer Sampson Moore.[34]
2007: Royal College of Surgeons of Edinburgh (RCSEd) King James IV 'Professorship' – a surgery prize with the courtesy title of professor for a year: this award was the first to be designated for ophthalmology.[35]
MacLaren, RE (2009). Learning and Teaching in Human Anatomy Applying current theories in educational research to medical student learning. Saarbrücken: VDM Verlag Dr. Müller. p.68. ISBN978-3639140538.
Retinitis pigmentosa (RP) is a member of a group of genetic disorders called inherited retinal dystrophy (IRD) that cause loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.
The National Eye Institute (NEI) is part of the U.S. National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services. The mission of NEI is "to eliminate vision loss and improve quality of life through vision research." NEI consists of two major branches for research: an extramural branch that funds studies outside NIH and an intramural branch that funds research on the NIH campus in Bethesda, Maryland. Most of the NEI budget funds extramural research.
Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye and causes it to thicken and swell (edema). The swelling may distort a person's central vision, because the macula holds tightly packed cones that provide sharp, clear, central vision to enable a person to see detail, form, and color that is directly in the centre of the field of view.
The Lions Eye Institute (LEI) is an Australian medical research institute affiliated with the University of Western Australia. It was established in 1983 with support of the Lions Clubs of Western Australia and headquartered in the Perth suburb of Nedlands, Western Australia. The LEI is a not-for-profit centre of excellence that combines an ophthalmic clinic with scientific discovery developing techniques for the prevention of blindness and the reduction of pain from blinding eye conditions.
A retinal implant is a visual prosthesis for restoration of sight to patients blinded by retinal degeneration. The system is meant to partially restore useful vision to those who have lost their photoreceptors due to retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Retinal implants are being developed by a number of private companies and research institutions, and three types are in clinical trials: epiretinal, subretinal, and suprachoroidal. The implants introduce visual information into the retina by electrically stimulating the surviving retinal neurons. So far, elicited percepts had rather low resolution, and may be suitable for light perception and recognition of simple objects.
Choroideremia is a rare, X-linked recessive form of hereditary retinal degeneration that affects roughly 1 in 50,000 males. The disease causes a gradual loss of vision, starting with childhood night blindness, followed by peripheral vision loss and progressing to loss of central vision later in life. Progression continues throughout the individual's life, but both the rate of change and the degree of visual loss are variable among those affected, even within the same family.
X-linked retinitis pigmentosa GTPase regulator is a GTPase-binding protein that in humans is encoded by the RPGR gene. The gene is located on the X-chromosome and is commonly associated with X-linked retinitis pigmentosa (XLRP). In photoreceptor cells, RPGR is localized in the connecting cilium which connects the protein-synthesizing inner segment to the photosensitive outer segment and is involved in the modulation of cargo trafficked between the two segments.
A visual prosthesis, often referred to as a bionic eye, is an experimental visual device intended to restore functional vision in those with partial or total blindness. Many devices have been developed, usually modeled on the cochlear implant or bionic ear devices, a type of neural prosthesis in use since the mid-1980s. The idea of using electrical current to provide sight dates back to the 18th century, discussed by Benjamin Franklin, Tiberius Cavallo, and Charles LeRoy.
The mission of the Foundation Fighting Blindness is to fund research that will lead to the prevention, treatment and cures for the entire spectrum of retinal degenerative diseases, including retinitis pigmentosa, macular degeneration, Usher syndrome, Stargardt disease and related conditions. These diseases, which affect more than 10 million Americans and millions more throughout the world, often lead to severe vision loss or complete blindness.
The Llura Liggett Gund Award honors researchers for career achievements that have significantly advanced the research and development of preventions, treatments and cures for eye disease.
Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.
The UCL Institute of Ophthalmology is an institute within the Faculty of Brain Sciences of University College London (UCL) and is based in London, United Kingdom. The institute conducts research and post-graduate teaching in the area of ophthalmology.
Gholam A. Peyman is an Iranian American ophthalmologist, retina surgeon, and inventor. He is best known for his invention of LASIK eye surgery, a vision correction procedure designed to allow people to see clearly without glasses. He was awarded the first US patent for the procedure in 1989.
Retinal regeneration refers to the restoration of vision in vertebrates that have suffered retinal lesions or retinal degeneration.
José-Alain Sahel is a French ophthalmologist and scientist. He is currently the chair of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, director of the UPMC Vision Institute, and the Eye and Ear Foundation Chair of Ophthalmology. Dr. Sahel previously led the Vision Institute in Paris, a research center associated with one of the oldest eye hospitals of Europe - Quinze-Vingts National Eye Hospital in Paris, founded in 1260. He is a pioneer in the field of artificial retina and eye regenerative therapies. He is a member of the French Academy of Sciences.
The Vision Institute is a research center in the Quinze-Vingts National Eye Hospital in Paris, France. It is one of several such centers in Europe on eye diseases.
Noemi Lois is a Clinical Professor of Ophthalmology at Queen's University Belfast and an Honorary Consultant Ophthalmologist and Vitreoretinal Surgeon at the Belfast Health and Social Care Trust.
Occult macular dystrophy (OMD) is a rare inherited degradation of the retina, characterized by progressive loss of function in the most sensitive part of the central retina (macula), the location of the highest concentration of light-sensitive cells (photoreceptors) but presenting no visible abnormality. "Occult" refers to the degradation in the fundus being difficult to discern. The disorder is called "dystrophy" instead of "degradation" to distinguish its genetic origin from other causes, such as age. OMD was first reported by Y. Miyake et al. in 1989.
Paul A. Sieving is a former director of the National Eye Institute, part of the U.S. National Institutes of Health. Prior to joining the NIH in 2001, he served on the faculty of the University of Michigan Medical School as the Paul R. Lichter Professor of Ophthalmic Genetics. He also was the founding director of the Center for Retinal and Macular Degeneration in the university's Department of Ophthalmology and Visual Sciences.
Intravitreal gene therapy represents an approach to treating retinal diseases by delivering therapeutic genes directly into the vitreous humor of the eye. This method uses a viral vector, often an adeno-associated virus (AAV), to carry genetic material into retinal cells. Once inside, the therapeutic genes are expressed to address genetic deficiencies or modify biological pathways, offering a long-term or potentially permanent treatment for conditions like wet age-related macular degeneration (AMD), diabetic macular edema, and inherited retinal dystrophies. Unlike traditional therapies requiring frequent injections, intravitreal gene therapy aims to reduce the treatment burden while improving efficacy potentially providing life long benefit.
↑ Stingl, K.; Bartz-Schmidt, K. U.; Besch, D.; Chee, C. K.; Cottriall, C. L.; Gekeler, F.; Groppe, M.; Jackson, T. L.; MacLaren, R. E.; Koitschev, A.; Kusnyerik, A.; Neffendorf, J.; Nemeth, J.; Naeem, M. A.; Peters, T.; Ramsden, J. D.; Sachs, H.; Simpson, A.; Singh, M. S.; Wilhelm, B.; Wong, D.; Zrenner, E. (8 June 2015). "Electronic Retina – Nuffield Department of Clinical Neurosciences". Vision Research. 111 (Pt B). University of Oxford: 149–60. doi:10.1016/j.visres.2015.03.001. PMID25812924. S2CID13949522. Retrieved 30 December 2016.
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