I Grierson

University of Liverpool, Liverpool, England, United Kingdom

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Publications (248)716.6 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing body of evidence has revealed that stem-like cells in the posterior limbus of the eye between the corneal endothelium (CE) and trabecular meshwork (TM) may be able to rejuvenate these tissues in disease. However, these cells have not been clearly defined and we have named them PET cells (Progenitor cells of the Endothelium and Trabeculum). A good and inexpensive animal model for PET cells is lacking, so we investigated bovine eyes as an effective large tissue source. We showed the presence of stem/progenitor cells in the bovine CE, transition zone and TM in situ. Floating spheres cultured from the CE and TM showed similar stem cell marker expression patterns. Both the CE and TM spheres were bipotent and highly proliferative, but with limited secondary sphere-forming capability. They were highly prone to differentiate back into the cell type of their tissue of origin. It is speculated that the PET cells become more tissue-specific as they migrate away from their niche. Here, we showed that PET cells are present in the posterior limbus of bovine eyes and that they can be successfully cultured and expanded. PET cells represent an attractive target for developing new treatments to regenerate both the CE and TM, thereby reducing the requirement for donor tissue for corneal transplant and invasive treatments for glaucomatous patients.
    No preview · Article · Oct 2014 · Stem Cells and Development
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    ABSTRACT: Abstract Purpose: In trabecular meshwork (TM) cells, actin geodesic arrangements were measured and then subjected to computational modeling to appreciate the response of different dome shapes to mechanical force. Methods: Polygonal actin arrangements (PAAs) and cross-linked actin networks (CLANs) were induced and imaged by Alexa Flour(®) 488 Phalloidin in bovine TM and human TM cells. Masked images were examined for size, circularity, and spoke and hub dimensions using ImageJ. Finite element modeling was used to create idealized dome structures and "realistic" PAA and CLAN models. The models were subjected to different loads simulating concentrated force and distortion measured. Results: We provide evidence that PAAs and CLANs are not identical. Both structures formed flattened domes but PAAs were 6 times larger than CLANs, significantly more circular and had greater height. The dimensions of the triangulations of hubs and spokes were, however, remarkably similar. Hubs were around 2 μm(2) in area, whereas spokes were about 5 μm in length. Our modeling showed that temporary arrangements of polygonal actin structures (TAPAS) were because of their flattened shape, more resistant to shearing than compression when compared with idealized domes. CLANs were marginally more resistant to shearing than PAAs but because of size much more resistant to compression. Conclusions: Evidence is provided that there are 2 types of actin icosahedrons in cultured TM cells we collectively call TAPAS. Modeling suggests that TAPAS have rigidity and are better at dealing with shearing than compression forces. The 2 types of TAPAS, PAAs, and CLANs, have much in common but there are size and mechanical response differences that need to be taken into account in future experimentation.
    No preview · Article · Jan 2014 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To assess the biocompatibility of a novel implant made of Nitinol (nickel-titanium alloy), designed to improve aqueous humor outflow. In the first arm of biocompatibility testing, microstents were surgically inserted into Schlemm's canal (SC) of 2 non-human primates (NHPs), and a third NHP served as a surgical sham control. After 13 weeks the animals were killed, and the eyes were examined by light and scanning electron microscopy. Two masked investigators evaluated the histology sections. The second arm utilized 8 New Zealand white rabbits; each rabbit received a microstent inserted into the sclera and subconjunctival space by means of passage across the anterior chamber thus providing contact with several representative ocular tissues. The fellow eye of each rabbit underwent a sham procedure without microstent insertion. The rabbits were killed after 26 weeks, and a trained ocular pathologist examined the specimens using light microscopy. Histologic and scanning electron microscopy analysis of the NHPs demonstrated that the microstents were located in SC. There was no evidence of an acute or chronic inflammatory response, granulation response, or fibrosis in the outflow system or in adjacent tissues. Rabbit eyes showed minimal mononuclear cell infiltration and minimal fibrotic responses at the site of the implants when compared with sham-treated control eyes. The Hydrus Microstent was associated with minimal inflammation in both NHP and rabbit eyes with extended follow-up. These preclinical studies demonstrate that the Hydrus Microstent appears to have excellent long-term biocompatibility.
    Full-text · Article · Nov 2013 · Journal of glaucoma
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    ABSTRACT: Several adult stem cell types have been found in different parts of the eye, including the corneal epithelium, conjunctiva, and retina. In addition to these, there have been accumulating evidence that some stem-like cells reside in the transition area between the peripheral corneal endothelium (CE) and the anterior nonfiltering portion of the trabecular meshwork (TM), which is known as the Schwalbe's Ring region. These stem/progenitor cells may supply new cells for the CE and TM. In fact, the CE and TM share certain similarities in terms of their embryonic origin and proliferative capacity in vivo. In this paper, we discuss the putative stem cell source which has the potential for replacement of lost and nonfunctional cells in CE diseases and glaucoma. The future development of personalized stem cell therapies for the CE and TM may reduce the requirement of corneal grafts and surgical treatments in glaucoma.
    Full-text · Article · Dec 2011 · BioMed Research International
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    ABSTRACT: It is well established that the unusual actin arrangements known as cross-linked actin networks (CLANs) can be induced by dexamethasone (DEX) in trabecular meshwork (TM) cells. Recent work reporting their presence in elderly glaucomatous and nonglaucomatous tissue, however, has highlighted the presence of other inducers. In this study, the authors sought to identify CLAN induction agents that may be present within and around the outflow system. Studies were conducted on confluent bovine TM (BTM) cells in culture, and actin was stained with Alexa-Fluor 488 phalloidin to identify CLANs in the target cells. The CLAN-inducing potential of aqueous humor was expanded and included investigation of transforming growth factor-beta 2 (TGF-β2). The effect of decorin and fetal calf serum (FCS) on BTM cell cytoskeleton was also investigated, and all were compared with DEX with an exposure period of up to 7 days. CLAN numbers were increased after 7 days of exposure to TGF-β2 (45%), aqueous humor (37%), and decorin (69%). Even FCS had some modest CLAN-inducing ability (reaching 12%) in BTM cells. Neutralization of TGF-β2 reduced CLAN incidence in aqueous humor conditions to baseline (12%) levels. Blocking TGF-β2 receptors reduced CLAN formation in TM cells by 25% to 30%, whereas the inhibition of Smad3 negated CLAN incidence. In this study the authors identified TGF-β2 as a CLAN-inducing component present in aqueous humor. Decorin was also implicated as another CLAN-inducing agent and it was confirmed that FCS has CLAN-inducing properties.
    Full-text · Article · Aug 2011 · Investigative ophthalmology & visual science
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    L Davies · D. D Spiller · M R H White · I Grierson · L Paraoan
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    ABSTRACT: The activation and regulation of target genes by the tumour-suppressor p53 dictates the fate of a cell, with cell cycle arrest or apoptosis being two distinct outcomes. PERP (p53 apoptosis effector related to PMP-22), a p53 transcriptional target, is induced specifically during apoptosis but not cell cycle arrest. Downregulation of PERP is associated with the aggressive, monosomy 3-type of uveal melanoma (UM), the most common primary intraocular tumour in adults, and increased PERP expression has a pro-apoptotic effect in UM cells. Here, we identify a novel effect of PERP expression, as elevated PERP protein positively influences active levels of its own transcriptional regulator, p53. Using fluorescent fusion proteins of PERP, p53 and MDM2, we demonstrate in single living UM cells that PERP expression significantly enhances p53 activity and its nuclear localization, increases p53-dependent transcription (including that of MDM2) while allowing oscillatory nucleo-cytoplasmic shuttling of p53/MDM2 complexes. Phosphorylation of p53 serine residues that interfere with the interaction between p53 and its negative regulator MDM2 and enhance pro-apoptotic gene transcription also occurs subsequent to PERP expression. These results implicate a role for PERP in amplifying functional p53 levels that promote p53-dependent apoptosis, and reveal a potential target for exploitation in enhancing p53 activity.
    Full-text · Article · Mar 2011 · Cell Death & Disease
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    ABSTRACT: Retinal pigment epithelial (RPE) transplantation presents a potential treatment for age-related macular degeneration (AMD). A suitable transplant membrane that can support an intact functioning RPE monolayer is required. Expanded polytetrafluoroethylene (ePTFE) possesses the physical properties required for a transplanting device; however, cells do not attach and spread on ePTFE. This study investigated the ability of surface-modified ePTFE to optimise the growth and function of healthy RPE monolayers. ePTFE discs were modified by ammonia gas plasma treatment. ARPE-19 cells were seeded on the membranes and maintained in media supplemented with retinoic acid and reduced serum. Cell number, morphology and proliferation were analysed. RPE monolayer function was investigated through formation of cell-cell junctions and phagocytosis of photoreceptor outer segments (POS). Ammonia gas plasma treatment resulted in enhanced cell growth and good monolayer formation with evidence of cell-cell junctional proteins. Furthermore, RPE monolayers were able to phagocytose POS in a time-dependent manner. ePTFE can be surface-modified to support an intact functional monolayer of healthy RPE cells with normal morphology and the ability to perform RPE-specific functions. Following further investigation ePTFE may be considered for use in transplantation.
    Full-text · Article · Feb 2011 · The British journal of ophthalmology

  • No preview · Article · Jan 2011
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    ABSTRACT: A study was undertaken to determine and compare the F-actin staining patterns in the cells of the lamina cribrosa (LC) of normal, dexamethasone (DEX)-treated and glaucomatous dissected tissue and cell cultures. About 30 dissected donor eyes and nine cell lines provided the human specimens; 25 eyes and 20 primary cell cultures provided the bovine material. Appropriate samples were exposed to 1×10⁻⁷ M DEX for up to 14 days. LC tissue and cells were stained with Phalloidin-Alexa 488 to identify F-actin, and all samples were examined by confocal or epifluorescent microscopy. Both in the LC tissue and LC cell cultures the dominant actin arrangement was bundles of stress fibres. However, cross-linked actin networks (CLANs) were identified in the tissue and in culture. These were markedly increased by steroid treatment and were particularly large and abundant in cultures from glaucoma donors. CLANs were not associated with optic nerve head astrocytes. The presence of abundant stress fibres in situ and in vitro highlights the biomechanical contribution of LC cells. However, the identification of CLANs in these cells shows that they are not exclusive to the trabecular meshwork, the only other place they have been found, and may have a role in glaucoma pathology.
    Full-text · Article · Oct 2010 · The British journal of ophthalmology
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    ABSTRACT: Cystatin C is a strong inhibitor of cysteine proteinases expressed by diverse cells. Variant B cystatin C, which was associated with increased risk of developing age-related macular degeneration, differs from the wild type protein by a single amino acid (A25T) in the signal sequence responsible for its targeting to the secretory pathway. The same variant conveys susceptibility to Alzheimer disease. Our investigations of the trafficking and processing of variant B cystatin C in living RPE cells highlight impaired secretion of extracellular modulators and inappropriate protein retention in RPE cells as potential molecular mechanisms underpinning macular, and possibly neuronal, degeneration.
    Full-text · Article · Nov 2009 · Vision research
  • C. A. Hitchins · I. Grierson
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    ABSTRACT: A morphological and autoradiographic assessment was made of scar tissue development in an experimental rabbit model of proliferative vitreoretinopathy which involves the intravitreal injection of cultured autologous skin fibroblasts. Within a few hours after injection as many as 40% of the cultured cells had autolysed. However, the remaining cells proliferated and formed membranes. The incorporation of [3H] thymidine was maximal at 1 week. Between 2 and 4 weeks spindle-shaped myofibroblasts were prominent, and this form of fibroblast has been considered to have an important role in scar tissue contraction. At the end of 4 weeks it was noted that all eyes had developed retinal detachments. Subsequently the membranes became progressively more fibrous and lipid-like material accumulated in the cytoplasm of many cells. The findings were discussed in relation to the use of this model to test the effectiveness of various drugs which may be of value in the treatment of proliferative vitreoretinopathy.
    No preview · Article · Oct 2009 · Acta Ophthalmologica
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    ABSTRACT: A cytoskeletal feature of human trabecular meshwork (HTM) cells in vitro and ex vivo is the presence of cross-linked actin networks (CLANs) that are abundant in a proportion of TM cells exposed to dexamethasone (DEX) and also in cells from glaucoma patients. We wished to determine whether CLANs were present in the bovine trabecular meshwork (BTM), whether they were similarly induced by dexamethasone and whether the structures were comparable to CLANs in HTM cells. Cultures of HTM and BTM cells and ex vivo dissections of BTM tissue were stained with phalloidin (F-actin) and propidium iodide (nuclei) and imaged by confocal microscopy, thereafter being subjected to image analysis. Some CLAN-like structures were identified in ex vivo BTM tissue cultured with and without DEX. However we found that BTM cells in culture produced abundant CLANs when exposed to DEX; comparable to the best response from HTM cells. The CLANs were of similar dimensions and morphology to those found in human cells and they had a similar half life of 2 or 3 days following the removal of DEX. This work demonstrates that BTM cells provide a suitable model for future investigations of CLAN formation and function. BTM cultures are sufficiently hardy to thrive in low serum and serum-free conditions so we were able to show that aqueous humor stimulates CLAN formation in the target cells. Future research is directed at identifying the aqueous component(s) responsible for CLAN production.
    Full-text · Article · Jul 2009 · Experimental Eye Research
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    ABSTRACT: Although well-acknowledged in vivo, spontaneous death of cancer cells in vitro is less widely appreciated. Colony formation was studied in untreated control plates of standard clonogenic assays and measurements of actual and potential doubling times performed in asynchronous cultures of human cancer cells lines. Western blotting of lung large cell carcinoma, COR-L23 cells actively undergoing spontaneous cell death was also carried out. Catastrophic disintegration of mature colonies could be seen in the untreated plates of lung large cell carcinoma, H460 and colon adenocarcinoma, SW620 human cancer cell lines and a significant cell loss factor was present in the cell lines growing as adherent cells in continuous culture. Western blotting demonstrated alterations of relative cyclin dependent kinase (Cdk)1 to Cdk4 protein expression in dying COR-L23 cells. The phenomenon of spontaneous cell death should be considered a hallmark of cancer and may be the result of failure to stabilise unstable, fully developed cancer cells due to the disruption of Cdk1/Cdk4 co-expression in those cells.
    No preview · Article · Jul 2009 · Anticancer research
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    C M Sheridan · S Mason · D M Pattwell · D Kent · I Grierson · R Williams
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    ABSTRACT: There are numerous scenarios in which replacing the diseased RPE monolayer is an attractive but as yet unrealised goal. The proof of concept that vision can be improved by placing a healthy neuroretina onto a different, healthy, underlying RPE layer is demonstrated in patch graft transplantations. The surgical procedure to relocate the neuroretina is both complex and is hampered by postoperative complications and as such newer replacement procedures are also being investigated including stem cell replacement therapies. Past studies have largely focused on using cell suspensions and have had disappointing outcomes largely due to the lack of control over cellular differentiation, incomplete attachment onto Bruch's membrane and subsequent integration into the existing RPE monolayer. The choice of which cells to transplant is still under investigation and is complicated by factors such as the ease of collection of an adequate sample, rejection following implantation, the age of the cells and ethical issues. In all these situations, however, understanding the mechanisms of cellular differentiation are likely to be prerequisite to future successes.The current research into replacing the RPE monolayer is briefly discussed with reference to our experiences comparing IPE and RPE cells in an in vitro environment.
    Full-text · Article · Feb 2009 · Eye (London, England)
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    ABSTRACT: The present study aimed to investigate, as a follow-up of microarray profiling, the expression of the lysosomal cysteine protease cathepsin S and that of its endogenous inhibitor cystatin C in the most common primary intraocular tumor in adults, uveal melanoma. The expression pattern unveiled was characterized by a relative increase in the active form of the elastolytic and collagenolytic cathepsin S that was not counterbalanced by the expression of its strongest endogenous inhibitor cystatin C in the aggressive, highly metastatic uveal melanomas. The study provides evidence for a novel correlation between a specific cysteine protease activity and the strongest predictive factor for metastatic behavior in primary uveal melanoma and documents the first investigation of both a specific protease activity and its endogenous inhibitor in uveal melanoma. The results indicate that the shift in the balance between cathepsin S and cystatin C may be part of deregulated proteolytic pathways contributing to the invasive phenotype of uveal melanoma.
    No preview · Article · Feb 2009 · Frontiers in Bioscience
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    ABSTRACT: p53 apoptosis effector related to PMP-22 (PERP) is a transcriptional target gene of p53 tumour suppressor that is specifically induced during apoptosis and not during cell cycle arrest. In primary uveal melanoma (UM), the most common intraocular malignancy in adults that has a reportedly unaffected signalling pathway upstream of and including p53, PERP expression is down-regulated in the metastatic monosomy 3-type tumours, compared with the less aggressive disomy 3-type tumours. Here, we demonstrate experimentally, by the use of full-length PERP-green fluorescent protein (GFP) fusions and real-time confocal microscopy, the intracellular targeting and plasma membrane localization of PERP in living UM cells and show that expression of PERP induces caspase-mediated apoptosis in UM cells. Induction of PERP expression in GFP-PERP-transfected UM cells leads to increased levels of cleaved caspase-8 forms, as well as to reduction of its full-length substrate Bid, but not to detectable processing of caspase-9. The levels of mature caspase-8, -9 and -3 proteins significantly correlate with PERP expression levels in primary UMs. Transcriptional profiling of PERP and caspase-8 in tumour specimens indicates that the positive association of PERP and caspase-8 proteins is a consequence of post-translational processing, most likely at the level of caspase-8 cleavage, and not of increased transcription of pro-caspase-8. We conclude that PERP expression leads to activation of an extrinsic receptor-mediated apoptotic pathway, with a possible subsequent engagement of the intrinsic apoptotic pathway. The findings underline the apoptotic pathway mediated by PERP as a critical mechanism employed by UM tumours to modulate susceptibility to apoptosis.
    Full-text · Article · Dec 2008 · Journal of Cellular and Molecular Medicine
  • Kathryn P.B. Cracknell · Ian Grierson
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    ABSTRACT: Topical application of prostaglandin (PG) analogues are currently the most commonly used intraocular pressure lowering drugs in glaucoma. They have been available since the mid 1990's, and are efficacious and generally well tolerated, the compliance rates are good due to the once a day application regime. The mode of action of PGs is by increasing the aqueous humour outflow primarily via the uveoscleral route, and also (but to a lesser degree) the conventional trabecular meshwork pathway. Increased outflow is primarily accomplished by remodelling the extracellular matrix components in both of the outflow pathways. PGs are associated with very few systemic side effects. The side effects of concern are all concentrated in the eye. Conjunctival hyperaemia is a common mild but transient complication. Since the development of this class of drug the most worrying and unusual side effect is a change in the pigmentation of the melanin-containing tissues close to the application site, i.e. eyelid skin, eyelashes and iris. As the prostaglandin induced iris darkening (PIID) is irreversible on cessation of the drugs it was of particular concern. We report here the findings from many studies which strongly indicate that there are no histopathological changes occurring in the iris tissue that has developed the darkening side effect. The only definitive change that has been detected in the cases of PIID is a small enlargement of the size of the existing melanin granule population and it has been shown that this change in melanin granule size is sufficient to account for the PIID. These findings point to the conclusion that the darkening developed following PG use is of a purely cosmetic effect with little or no serious consequences.
    No preview · Article · Nov 2008 · Experimental Eye Research
  • Albert Alm · Ian Grierson · M Bruce Shields
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    ABSTRACT: Topical prostaglandin analogs, which have become first-line therapy in the medical management of glaucoma, have an excellent safety profile with regard to systemic side effects, but are associated with several ocular side effects. Some of these are common, with no apparent serious consequences other than cosmetic, whereas others are much less common but represent potentially sight-threatening side effects. The former group includes conjunctival hyperemia, elongation and darkening of eyelashes, induced iris darkening, and periocular skin pigmentation. The latter group of side effects, which are relatively rare and lack definitive causal relationship to prostaglandin analog therapy, includes iris cysts, cystoid macular edema, anterior uveitis, and reactivation of herpes simplex keratitis. Most of the literature regarding side effects associated with prostaglandin analogs involves the use of latanoprost, probably because it was the first to be studied. There is no evidence, however, aside from less conjunctival hyperemia with latanoprost, that the commercially available prostaglandin analogs differ significantly with regard to side effects.
    No preview · Article · Nov 2008 · Survey of Ophthalmology
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    ABSTRACT: A percentage of trabecular meshwork (TM) cells in tissue and organ culture have been shown to contain cross-linked actin networks (CLANs) when exposed to dexamethasone, as have TM cultures derived from glaucomatous individuals. The purpose of this study was to determine whether CLANs exist within TM cells in situ in tissue unmanipulated by culturing, thereby eliminating the possibility that CLANs are artifacts of culture conditions, and to determine their numbers and dimensions in normal and glaucoma TM cells. Twelve human donor eyes (five normal and seven with glaucoma) provided the TM tissue. Each eye was dissected, and the TM tissue was exposed either by microdissection (qualitative studies) or cryo-sectioning (quantitative analysis). The actin cytoskeleton was visualized using a high-affinity probe and viewed using confocal microscopy. Qualitative examination of the microdissected tissue revealed that CLANs and CLAN-like structures were a common finding in the TM cells in every specimen, irrespective of whether they were from normal or glaucomatous eyes. CLAN size and phenotype were variable, with the same variations occurring in both normal and glaucomatous eyes. Quantitative analysis showed that there were more CLANs in glaucoma TM specimens than normal TM specimens, but this difference was not statistically significant. The mean number of CLANs/TM cell in our glaucoma tissue was estimated to be 1.03, while in the elderly normal controls it was 0.67. This study showed for the first time that CLANs exist in cells of TM tissues from both normal and glaucomatous eyes that have not been manipulated by either tissue or organ culture procedures. It also provides quantitative data on CLAN prevalence in organized TM tissue, which indicates that CLANs are far more common than predicted (even from tissue culture) and there may be one in every cell in the glaucomatous TM in situ.
    No preview · Article · Nov 2008 · Investigative ophthalmology & visual science
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    ABSTRACT: Purpose:  To document the outcome of viscocanalostomy (VC) alone or combined with phacoemulsification (phaco-VC) in eyes with pseudoexfoliation glaucoma (PEXG) and primary open angle glaucoma (POAG).Methods:  A prospective, comparative study of 314 eyes undergoing VC in two centres over 6 years was conducted. Main outcome measures were: (i) intraocular pressure (IOP) control (complete success was IOP ≤ 18 mmHg without medication and failure IOP > 18 mmHg); and (ii) requirement for Nd:YAG laser goniopuncture (YAG-GP) if IOP > 21 mmHg.Results:  In the POAG group, 174 eyes underwent phaco-VC and 104 VC. In the PEX group, 20 eyes underwent phaco-VC and 16 VC. At final follow up, complete success rate (CSR) was 76% for POAG phaco-VC, 67% for POAG VC, 95% for PEXG phaco-VC and 63% for PEXG VC with mean IOP reduction of 29.9%, 40%, 42.5% and 51%, respectively. Without YAG-GP, by 3 years postoperatively the failure rate was 100% for PEXG eyes and 21% for POAG eyes undergoing VC alone, but PEXG eyes undergoing phaco-VC were 100% successful. CSR for YAG-GP was 92% in PEXG VC eyes and 55% in POAG VC eyes.Conclusions:  In phakic eyes with PEXG undergoing VC, an absolute requirement for long-term success was YAG-GP. This was not the case in POAG eyes or PEXG eyes undergoing phaco-VC. Late IOP rise in phakic PEXG eyes and restoration of IOP control following YAG-GP suggests that continued release of PEX material from the lens capsule with time blocks the outflow through the trabecular-Descemetic window created by VC.
    Full-text · Article · Feb 2008 · Clinical and Experimental Ophthalmology

Publication Stats

7k Citations
716.60 Total Impact Points


  • 1994-2014
    • University of Liverpool
      • • Department of Eye and Vision Science
      • • Department of Clinical Sciences
      • • School of Medicine
      Liverpool, England, United Kingdom
  • 2009
    • University of Nottingham
      • School of Clinical Sciences
      Nottigham, England, United Kingdom
  • 1993-2008
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
      • Department of Medicine
      Liverpool, England, United Kingdom
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
  • 2002
    • Liverpool Hospital
      Liverpool, New South Wales, Australia
  • 2000
    • University of South Wales
      Понтиприте, Wales, United Kingdom
  • 1981-1994
    • Moorfields Eye Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 1981-1991
    • London Research Institute
      Londinium, England, United Kingdom
  • 1989
    • University of Florida
      • Department of Ophthalmology
      Gainesville, Florida, United States
  • 1985-1988
    • UK Department of Health
      Londinium, England, United Kingdom
  • 1980-1986
    • University of London
      Londinium, England, United Kingdom
  • 1973-1979
    • University of Glasgow
      Glasgow, Scotland, United Kingdom