Publications
226 results found
Bizrah M, Dakin SC, Guo L, et al., 2014, A semi-automated technique for labeling and counting of apoptosing retinal cells, BMC Bioinformatics, Vol: 15, ISSN: 1471-2105
BackgroundRetinal ganglion cell (RGC) loss is one of the earliest and most important cellular changes in glaucoma. The DARC (Detection of Apoptosing Retinal Cells) technology enables in vivo real-time non-invasive imaging of single apoptosing retinal cells in animal models of glaucoma and Alzheimer’s disease. To date, apoptosing RGCs imaged using DARC have been counted manually. This is time-consuming, labour-intensive, vulnerable to bias, and has considerable inter- and intra-operator variability.ResultsA semi-automated algorithm was developed which enabled automated identification of apoptosing RGCs labeled with fluorescent Annexin-5 on DARC images. Automated analysis included a pre-processing stage involving local-luminance and local-contrast “gain control”, a “blob analysis” step to differentiate between cells, vessels and noise, and a method to exclude non-cell structures using specific combined ‘size’ and ‘aspect’ ratio criteria. Apoptosing retinal cells were counted by 3 masked operators, generating ‘Gold-standard’ mean manual cell counts, and were also counted using the newly developed automated algorithm. Comparison between automated cell counts and the mean manual cell counts on 66 DARC images showed significant correlation between the two methods (Pearson’s correlation coefficient 0.978 (p < 0.001), R Squared = 0.956. The Intraclass correlation coefficient was 0.986 (95% CI 0.977-0.991, p < 0.001), and Cronbach’s alpha measure of consistency = 0.986, confirming excellent correlation and consistency. No significant difference (p = 0.922, 95% CI: −5.53 to 6.10) was detected between the cell counts of the two methods.ConclusionsThe novel automated algorithm enabled accurate quantification of apoptosing RGCs that is highly comparable to manual counting, and appears to minimise operator-bias, whilst bei
Georgiou AL, Guo L, Cordeiro MF, et al., 2014, Electroretinogram and Visual-Evoked Potential Assessment of Retinal and Central Visual Function in a Rat Ocular Hypertension Model of Glaucoma, CURRENT EYE RESEARCH, Vol: 39, Pages: 472-486, ISSN: 0271-3683
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- Citations: 22
Davis BM, Normando EM, Guo L, et al., 2014, Topical delivery of Avastin to the posterior segment of the eye In vivo using annexin A5-associated liposomes, Small, Vol: 10, Pages: 1575-1584, ISSN: 1613-6810
Effective delivery to the retina is presently one of the most challenging areas in drug development in ophthalmology, due to anatomical barriers preventing entry of therapeutic substances. Intraocular injection is presently the only route of administration for large protein therapeutics, including the anti‐Vascular Endothelial Growth Factors Lucentis (ranibizumab) and Avastin (bevacizumab). Anti‐VEGFs have revolutionised the management of age‐related macular degeneration and have increasing indications for use as sight‐saving therapies in diabetes and retinal vascular disease. Considerable resources have been allocated to develop non‐invasive ocular drug delivery systems. It has been suggested that the anionic phospholipid binding protein annexin A5, may have a role in drug delivery. In the present study we demonstrate, using a combination of in vitro and in vivo assays, that the presence of annexin A5 can significantly enhance uptake and transcytosis of liposomal drug carrier systems across corneal epithelial barriers. This system is employed to deliver physiologically significant concentrations of Avastin to the posterior of the rat eye (127 ng/g) and rabbit retina (18 ng/g) after topical application. Our observations provide evidence to suggest annexin A5 mediated endocytosis can enhance the delivery of associated lipidic drug delivery vehicles across biological barriers, which may have therapeutic implications.
Bono V, Davis BM, Normando EM, et al., 2014, Comparison of global visual field indices (MD, VFI), GPA II change and cluster analysis of visual field progression in glaucoma, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Azarbod P, Holder R, Crawley L, et al., 2014, An audit of ICare rebound tonometry in a tertiary glaucoma centre, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Guo L, Davis BM, Nizari S, et al., 2014, Direct optic nerve sheath (DONS) transplantation of Schwann cells reduces RGC death after optic nerve injury, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Davis BM, Normando EM, Guo L, et al., 2014, Topical Delivery of Avastin to the Posterior Segment of the Eye in vivo using Annexin A5-associated Liposomes, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Galvao J, Davis B, Tilley M, et al., 2014, Unexpected low-dose toxicity of the universal solvent DMSO, The FASEB Journal, Vol: 28, Pages: 1317-1330, ISSN: 0892-6638
Dimethyl sulfoxide (DMSO) is an important aprotic solvent that can solubilize a wide variety of otherwise poorly soluble polar and nonpolar molecules. This, coupled with its apparent low toxicity at concentrations <10%, has led to its ubiquitous use and widespread application. Here, we demonstrate that DMSO induces retinal apoptosis in vivo at low concentrations (5 μl intravitreally dosed DMSO in rat from a stock concentration of 1, 2, 4, and 8% v/v). Toxicity was confirmed in vitro in a retinal neuronal cell line, at DMSO concentrations >1% (v/v), using annexin V, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), and AlamarBlue cell viability assays. DMSO concentrations > 10% (v/v) have recently been reported to cause cellular toxicity through plasma membrane pore formation. Here, we show the mechanism by which low concentrations (2–4% DMSO) induce caspase‐3 independent neuronal death that involves apoptosis‐inducing factor (AIF) translocation from mitochondria to the nucleus and poly‐(ADP‐ribose)‐polymerase (PARP) activation. These results highlight safety concerns of using low concentrations of DMSO as a solvent for in vivo administration and in biological assays. We recommend that methods other than DMSO are employed for solubilizing drugs but, where no alternative exists, researchers compute absolute DMSO final concentrations and include an untreated control group in addition to DMSO vehicle control to check for solvent toxicity.—Galvao, J., Davis, B., Tilley, M., Normando, E., Duchen, M. R., Cordeiro, M. F. Unexpected low‐dose toxicity of the universal solvent DMSO. FASEB J. 28, 1317–1330 (2014). www.fasebj.org
Hanumunthadu D, Dehabadi MH, Cordeiro MF, 2014, Neuroprotection in glaucoma: Current and emerging approaches, Expert Review of Ophthalmology, Vol: 9, Pages: 109-123, ISSN: 1746-9899
Neuroprotection in glaucoma aims to prevent degeneration of RGCs, independent of reduction in intraocular pressure, in order to maintain visual function. The vast potential for neuroprotection to prevent decline in visual function and preserve quality of life has stimulated research into multiple therapeutic approaches. Current strategies have focused on drug therapies that have the ability to preserve visual function by prevention of RGC apoptosis. There is promise in new treatments in stem cell and gene therapy. Despite such innovation, there has been a delay in translating research from bench to the clinic; conventional clinical trial designs in glaucoma have proven to be lengthy, expensive and difficult to define. This review highlights new and emerging approaches in neuroprotection for glaucoma. Additionally, it explores the ability of alternative clinical trial design to investigate therapeutic concepts and facilitate the development of novel therapy for patients. © 2014 Informa UK Ltd.
Dehabadi MH, Davis BM, Wong TK, et al., 2014, Retinal manifestations of Alzheimer's disease., Neurodegener Dis Manag, Vol: 4, Pages: 241-252
Alzheimer's disease (AD) is neurodegenerative condition and most common cause of dementia worldwide. Current criteria for its diagnosis and monitoring rely on subjective, expensive or invasive methods that lack sufficient sensitivity, such that a concrete diagnosis of AD can only be made postmortem. Given the structural similarities of the neuro-retina and central nervous system, researchers have shown many manifestations of AD to be detectible in the retinae of humans and transgenic models of AD. Due to the eye's unique optical properties allowing noninvasive in vivo imaging, the retina could provide a window for the early diagnosis and monitoring of AD long before symptom manifestation.
Clement CI, Kampougeris G, Ahmed F, et al., 2013, Combining phacoemulsification with endoscopic cyclophotocoagulation to manage cataract and glaucoma, CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, Vol: 41, Pages: 546-551, ISSN: 1442-6404
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- Citations: 44
Normando EM, Turner LA, Cordeiro MF, 2013, The potential of annexin-labelling for the diagnosis and follow-up of glaucoma, CELL AND TISSUE RESEARCH, Vol: 353, Pages: 279-285, ISSN: 0302-766X
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- Citations: 16
Cordeiro MF, Goldberg I, Schiffman R, et al., 2013, Efficacy of a preservative-free fixed combination of bimatoprost and timolol in treatment-naive versus previously treated patients, ACTA OPHTHALMOLOGICA, Vol: 91, ISSN: 1755-375X
Normando E, Turner L, Ahmed F, et al., 2013, Objective Assessment of Glaucoma Suspect Comparing Different Imaging Techniques, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Kersey T, Clement CI, Bloom P, et al., 2013, New trends in glaucoma risk, diagnosis & management, INDIAN JOURNAL OF MEDICAL RESEARCH, Vol: 137, Pages: 659-668, ISSN: 0971-5916
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- Citations: 19
Stalmans I, Megevand GS, Cordeiro MF, et al., 2013, Preservative-free treatment in glaucoma: who, when, and why?, EUROPEAN JOURNAL OF OPHTHALMOLOGY, Vol: 23, Pages: 518-525, ISSN: 1120-6721
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- Citations: 35
Galvao J, Davis BM, Cordeiro MF, 2013, <i>In vivo</i> imaging of retinal ganglion cell apoptosis, CURRENT OPINION IN PHARMACOLOGY, Vol: 13, Pages: 123-127, ISSN: 1471-4892
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- Citations: 18
Normando EM, Tilley M, Guo L, et al., 2013, Imaging in DRY AMD, Drug Discovery Today: Therapeutic Strategies, Vol: 10, Pages: e35-e41
Since the discovery of fluorescein angiography much progress has been made in the field of retinal imaging. For age-related macular degeneration in particular, the scientific and clinical communities are facing a revolution in diagnostic tools. Confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography have enabled the non-invasive visua-lization of the natural history of a disease. With the advent of adaptive optics it is now also possible to resolve the fine structure of the photoreceptor mosaic, giving new perspective to the understanding of future potential therapeutic strategies.
Georgiou AL, Guo L, Cordeiro MF, et al., 2012, Changes in the modulation of retinocollicular transmission through group III mGluRs long after an increase in intraocular pressure in a rat model of glaucoma, VISUAL NEUROSCIENCE, Vol: 29, Pages: 237-246, ISSN: 0952-5238
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- Citations: 5
Parnell M, Guo L, Abdi M, et al., 2012, Ocular manifestations of Alzheimer's disease in animal models, International Journal of Alzheimer's Disease, Vol: 2012, ISSN: 2090-8024
Alzheimer's disease (AD) is the most common form of dementia, and the pathological changes of senile plaques (SPs) and neurofibrillary tangles (NFTs) in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an extension of the brain; the retina. Due to the optically transparent nature of the eye, it is possible to image the retina at a cellular level noninvasively and thus potentially allow an earlier diagnosis as well as a way of monitoring progression and treatment effects. Transgenic animal models expressing amyloid precursor protein (APP) presenilin (PS) and tau mutations have been used successfully to recapitulate the pathological findings of AD in the brain. This paper will cover the ocular abnormalities that have been detected in these transgenic AD animal models.
Butt GF, Habib A, Mahgoub K, et al., 2012, Optic nerve regeneration, Expert Review of Ophthalmology, Vol: 7, Pages: 533-554, ISSN: 1746-9899
Optic nerve injury is a consequence of numerous ophthalmic conditions including glaucoma, a leading cause of global blindness. In adult humans, the optic nerve displays limited regenerative capacity, typical of neurons of the CNS. In efforts to address this issue, a number of recent advances have been made in the identification of potential therapeutic targets that directly inhibit or stimulate optic nerve regeneration, with more work implicating several other factors. These factors can be categorized as being intracellular or extracellular with respect to the neuron, or inflammatory cell-derived. In addition to these therapeutic strategies, it is important to guide the regrowing axons to their correct destination. Recent work has identified several developmental guidance factors important in regeneration, and potential therapeutic targets for the future. This review discusses newly identified and existing regeneration factors and evaluates current cellular- and nanotechnology-based therapies that aim to aid and guide optic nerve regeneration to achieve functional recovery. © 2012 2012 Expert Reviews Ltd.
Crawley L, Zamir SM, Cordeiro MF, et al., 2012, Clinical options for the reduction of elevated intraocular pressure., Ophthalmol Eye Dis, Vol: 4, Pages: 43-64, ISSN: 1179-1721
Elevated IOP in clinical practice is usually seen in glaucoma or ocular hypertension. Glaucoma affects 60 million people worldwide and 8.4 million are bilaterally blind from this chronic disease.1 Options for reducing IOP rely on pharmacological agents, laser treatments and surgery which may be penetrating or non-penetrating. The last twenty years has seen significant changes in all of these strategies. This review aims to cover these clinical options and introduce some of the new technologies currently in development for the clinical lowering of IOP.
Clement C, Ahmed F, Cordeiro MF, et al., 2011, COMBINED PHACOEMULSIFICATION AND ENDOSCOPIC CYCLODIODE PHOTOCOAGULATION FOR THE MANAGEMENT OF CATARACT AND GLAUCOMA, Publisher: WILEY-BLACKWELL, Pages: 42-43, ISSN: 1442-6404
Cordeiro MF, Levin LA, 2011, Clinical Evidence for Neuroprotection in Glaucoma, AMERICAN JOURNAL OF OPHTHALMOLOGY, Vol: 152, Pages: 715-716, ISSN: 0002-9394
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- Citations: 33
Bizrah M, Guo L, Cordeiro MF, 2011, Glaucoma and Alzheimer's disease in the elderly, Aging Health, Vol: 7, Pages: 719-733, ISSN: 1745-509X
Primary open angle glaucoma and Alzheimer's disease have long been established as two separate pathological entities, primarily affecting the elderly. The progressive, irreversible course of both diseases has significant implications on an aging population. As the complex pathophysiology of the two diseases has progressively unraveled over the past two decades, common pathophysiological changes have also been elucidated. Some of these mechanisms have established a strong grounding, whilst others remain principally speculative. The mutual neuropathological changes in primary open angle glaucoma and Alzheimer's disease have facilitated the development of neuroprotective strategies. While most of these strategies are still in the preclinical phase, they have shown great promise in experimental animal studies. Further understanding of the common pathophysiology of primary open angle glaucoma and Alzheimer's disease and their timeline may have great implications on early diagnosis and effective therapeutic targeting. © 2011 Future Medicine Ltd.
Schmitz-Valckenberg S, Lara D, Nizari S, et al., 2011, Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging, BRITISH JOURNAL OF OPHTHALMOLOGY, Vol: 95, Pages: 1134-1139, ISSN: 0007-1161
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- Citations: 39
Cordeiro MF, Migdal C, Bloom P, et al., 2011, Imaging apoptosis in the eye, EYE, Vol: 25, Pages: 545-553, ISSN: 0950-222X
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- Citations: 50
Liu M, Duggan J, Salt TE, et al., 2011, Dendritic changes in visual pathways in glaucoma and other neurodegenerative conditions, EXPERIMENTAL EYE RESEARCH, Vol: 92, Pages: 244-250, ISSN: 0014-4835
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- Citations: 46
Coxon KM, Duggan J, Cordeiro MF, et al., 2011, Purification of annexin V and its use in the detection of apoptotic cells., Methods Mol Biol, Vol: 731, Pages: 293-308
Cell death by apoptosis has been studied for many years using fluorescently labeled annexin V. Annexin V shows high affinity for the phosphatidylserine that becomes enriched in the outer leaflet of the plasma membrane during apoptosis, but not necrosis, allowing differentiation between the two types of cell death. In this chapter we detail two methods for the purification of annexin V. The first is an untagged recombinant protein using a three step Fast Protein Liquid Chromatography (FPLC) method, and the second using a single step purification protocol via a glutathione S-transferase (GST) tag. Labeling of the resulting annexin V with a fluorescent dye to allow visualization of the protein is also explained. Finally, two methods are described in which a fluorescently labeled derivative of annexin V is used to detect apoptosis, namely the in vitro method of fluorescence-activated cell sorting (FACS) where fluorescent annexin V is used to differentiate apoptotic and necrotic cells within a population; and detection of apoptosing retinal cells (DARC) allowing the identification of apoptotic cells in the retina in vivo.
Coxon KM, Duggan J, Cordeiro MF, et al., 2011, Purification of Annexin V and Its Use in the Detection of Apoptotic Cells, CANCER CELL CULTURE: METHODS AND PROTOCOLS, SECOND EDITION, Vol: 731, Pages: 293-308, ISSN: 1064-3745
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- Citations: 14
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