ORCID Profile
0000-0002-3096-4682
Current Organisation
University of Oxford
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Publisher: American Medical Association (AMA)
Date: 08-2017
Publisher: Springer Science and Business Media LLC
Date: 18-06-2018
Publisher: Springer Science and Business Media LLC
Date: 10-2018
Publisher: SAGE Publications
Date: 05-2012
Abstract: Degeneration of the neural retina is the leading cause of untreatable blindness in the developed world. Stem cell replacement therapy offers a novel strategy for retinal repair. Postmitotic photoreceptor precursors derived from the early postnatal (P) retina are able to migrate and integrate into the adult mouse retina following transplantation into the subretinal space, but it is likely that a large number of these cells would be required to restore vision. The adult recipient retina presents a very different environment to that from which photoreceptor precursor donor cells isolated from the developing postnatal retina are derived. Here we considered the possibility that modulation of the recipient environment by ectopic expression of developmentally regulated growth factors, normally present during photoreceptor development, might enhance the migration and integration of transplanted cells into the adult neural retina. Adeno-associated viral (AAV) vectors were used to introduce three growth factors previously reported to play a role in photoreceptor development, IGF1, FGF2, and CNTF, into the adult retina, prior to transplantation of P4 cells derived from the Nrl.GFP + ve neural retina. At 3 weeks posttransplantation the number of integrated, differentiated photoreceptor cells present in AAV-mediated neurotrophic factor-treated eyes was assessed and compared to control treated contralateral eyes. We show, firstly, that it is possible to manipulate the recipient retinal microenvironment via rAAV-mediated gene transfer with respect to these developmentally relevant growth factors. Moreover, when combined with cell transplantation, AAV-mediated expression of IGF1 led to significantly increased levels of cell integration, while overexpression of FGF2 had no significant effect on integrated cell number. Conversely, expression of CNTF led to a significant decrease in cell integration and an exacerbated glial response that led to glial scarring. Together, these findings demonstrate the importance of the extrinsic environment of the recipient retina for photoreceptor cell transplantation and show for the first time that it is possible to manipulate this environment using viral vectors to influence photoreceptor transplantation efficiency.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Public Library of Science (PLoS)
Date: 06-03-2012
Publisher: Springer New York
Date: 30-11-2018
Publisher: Public Library of Science (PLoS)
Date: 24-04-2012
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-05-2016
DOI: 10.1167/TVST.5.3.10
Publisher: Elsevier BV
Date: 2017
Publisher: Wiley
Date: 04-2009
DOI: 10.1111/J.1442-9071.2009.01915.X
Abstract: To describe the 2- to 4-year visual and microperimetry outcomes of autologous retinal pigment epithelium (RPE)-choroid graft in patients with neovascular age-related macular degeneration (AMD). In this retrospective cohort study, 12 patients with subfoveal neovascular AMD who had undergone autologous RPE-choroid graft between August 2004 and June 2005 were reviewed. Change in visual acuity (VA), contrast sensitivity (CS), fixation stability and retinal sensitivity on microperimetry after 2-3 years and the rates of late postoperative complications were examined. Patients were followed for 26-48 months (mean, 39). Median preoperative VA (logMAR) was 0.87 but declined to 1.43 (1 year), 1.46 (2 years) and 1.38 (3 years), P = 0.001. Median CS (logCS) was 0.75 preoperatively but declined to 0.45 at 2 years. Six patients had serial microperimetry. Fixation stability declined in 1 but improved in 2 patients. All 6 had decline in retinal sensitivity over the graft during follow up. Retinal detachment did not occur after 12 months but 8 developed epiretinal membrane, 12 had cystic retinal change over the graft and 4 developed recurrent choroidal neovascularization. However, 10 grafts retained autofluorescence signal at 18-48 months of follow up. Autologous RPE-choroid graft can maintain VA, stable fixation and retinal sensitivity in some patients for over 3 years. The spatial correlation between graft autofluorescence, outer retinal structures on optical coherence tomography and retinal sensitivity are consistent with photoreceptor cell rescue. However, we caution the use of this technique as there is high complication rate and delayed loss of retinal function.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Springer Science and Business Media LLC
Date: 16-11-2017
DOI: 10.1038/GT.2017.85
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-12-2015
Publisher: SLACK, Inc.
Date: 12-2017
DOI: 10.3928/23258160-20171130-06
Abstract: The aim of this study was to assess changes in retinal structure and thickness after subretinal implantation of the Retina Implant Alpha IMS (Retina Implant AG, Reutlingen, Germany). Spectral-domain optical coherence tomography (SD-OCT) imaging was performed to assess the structure and thickness of the retina anterior to the microphotodiode array preoperatively, within 6 weeks and 6 months ± 1 month after implantation. Thickness measurements were performed using the distance tool of the built-in software. Three thickness measurements were performed in each of the four quadrants of the retina on the microchip within 6 weeks and 6 months ± 1 month after implantation. The mean ± standard deviation change in retinal thickness from within 6 weeks to 6 months ± 1 month after implantation in all four quadrants combined was 24 μm ± 68 μm. None of the tested variables (location, time, or their interaction) had a statistically significant effect on the mean retinal thickness ( P = .961, P = .131, and P = .182, respectively n = 19). The authors report on qualitative and quantitative findings in retinal structure in 27 patients after subretinal implantation of the Retina Implant Alpha IMS using OCT technology. No significant changes of retinal thickness could be observed in a period of 6 months after surgery. With more patients receiving subretinal implants and with advanced OCT technology, the data set will be extended to study possible changes in retinal structure in finer detail. [ Ophthalmic Surg Lasers Imaging Retina . 2017 :993–999.]
Publisher: Elsevier BV
Date: 03-2018
Publisher: Hindawi Limited
Date: 29-06-2021
DOI: 10.1002/HUMU.24242
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-11-2016
Publisher: Frontiers Media SA
Date: 23-08-2017
Publisher: Elsevier BV
Date: 06-2015
Publisher: Massachusetts Medical Society
Date: 19-05-2016
DOI: 10.1056/NEJMC1509501
Publisher: Wiley
Date: 19-04-2017
DOI: 10.1111/CGE.13021
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 30-10-2017
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.OPHTHA.2009.10.046
Abstract: Enhanced S-cone syndrome (ESCS), also known as Goldmann-Favre syndrome, is a progressive retinal degeneration that frequently presents with night blindness and nummular pigment clumping around the vascular arcades and is caused by recessive mutations in the photoreceptor-specific NR2E3 transcription factor. A unique feature of this disease is the development of retinoschisis of the macula. This study used fine anatomic and functional assessments within this region to determine whether the loss of retinal function was due to progressive schisis or a primary photoreceptor loss, similar to other rod-cone dystrophies. Cross-sectional, prospective study. Nine probands (n=18 eyes) and 3 controls (n=6 eyes) were studied at Moorfields Eye Hospital in London, United Kingdom. Histories were obtained and visual acuity was measured using Early Treatment Diabetic Retinopathy Study protocol. Autofluorescence (AF), fundus photography, and spectral domain optical coherence tomography (OCT) imaging were co-registered to detailed microperimetry (Nidek MP1 NAVIS software version 1.7.2 Nidek Technologies, Padova, Italy) data for statistical analysis. Retinal sensitivity (decibels) in a customized test grid of the macula retinal structure assessed with OCT and AF. Patients were ided into 3 cohorts roughly based on life span and documentation of schisis: (1) no schisis, childhood (2) macular schisis, young adults (3) resolved schisis, older adults. Retinal sensitivity was significantly attenuated in those with schisis and did not recover in those whose schisis had resolved despite retinal thickness comparable to that of controls. All probands exhibited loss of AF peripherally (and corresponding loss of retinal sensitivity), but there was relative preservation of AF within the macula. Development of macular retinoschisis in ESCS is an important feature of the disease and contributes to attenuated retinal sensitivity that persists after resolution of retinoschisis. The central macula appears to be compromised more by foveoschisis than photoreceptor loss. In contrast, the peripheral retina (ordinarily a rod-rich region) is affected early in the disease process and degenerates rapidly because of photoreceptor loss. Thus, 2 distinct mechanisms of retinal degeneration may exist in ESCS, corresponding to regions of the retina that may experience either normal or abnormal photoreceptor development.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-07-2016
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 29-08-2016
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 02-2017
Publisher: American Medical Association (AMA)
Date: 03-2017
DOI: 10.1001/JAMAOPHTHALMOL.2016.5630
Abstract: The early decline and recovery of retinal structure and function following iatrogenic macular detachment for retinal gene therapy is not well characterized in those with relatively preserved central visual function. Here, the recovery of retinal structure and function over the first month following iatrogenic retinal detachment for the delivery of adeno-associated viral vector encoding Rab Escort Protein 1 is described as a part of gene therapy for choroideremia. To study changes in both retinal structure and function during the first month following iatrogenic macular detachment surgery. This prospective interocularly controlled study was conducted between February 1 and December 31, 2015. Treatment consisted of a subretinal injection of 0.1 mL of a gene therapy solution containing 1 × 1011 viral particles performed unilaterally. The participants were 5 males, aged 23 to 71 years, with a clinical and genetic diagnosis of choroideremia. Retinal structure and function were assessed at baseline, 1 week, and 1 month using optical coherence tomography, logMAR visual acuity, microperimetry, the Farnsworth-Munsell (FM) 100-hue test, and the Rayleigh match. Five white male patients aged 23 to 71 years underwent unilateral subretinal gene therapy for genetically confirmed choroidermeia. Optical coherence tomographic images demonstrated a complete resolution of the resulting iatrogenic retinal detachment by 1 week in all 5 patients. At 1 month, the mean (SE) change in central foveal thickness was +9.6 (7.2) μm in treated eyes and +8.8 (12.6) μm in control eyes. The mean (SE) change in visual acuity was +5.4 (3.3) letters in treated eyes and +0.8 (3.1) letters in control eyes. At 1 month, the mean (SE) threshold sensitivity changes were -1.2 (2.1) dB in treated eyes and -1.0 (1.2) dB in control eyes. Color discrimination at the FM 100-hue changed little at 1 month (mean [SE] change in C-index, -0.2 [0.4] in treated eyes and 0.1 [0.2] in control eyes). Rayleigh matches in 1 patient were consistent with a diagnosis of pseudoprotanomaly, suggesting decreased effective optical density of the cone photopigments. Retinal structural recovery-as assessed by optical coherence tomography-occurs soon after iatrogenic detachment. Similarly, visual acuity recovers or improves within 1 month of the procedure and may not be accompanied by improvements in threshold sensitivity or color discrimination. Changes in color matching in 1 patient suggest decreased optical density of the cone photopigments in the early postoperative period.
Publisher: Springer Science and Business Media LLC
Date: 16-01-2015
DOI: 10.1038/EYE.2014.326
Publisher: Elsevier BV
Date: 05-2022
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Robert MacLaren.