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Kamalden T.A.,University of Oxford | Ji D.,University of Oxford | Osborne N.N.,University of Oxford | Osborne N.N.,Instituto Oftalmologico Fernandez Vega
Neurochemical Research | Year: 2012

The aim of the present studies was to characterise cell death following inhibition of mitochondrial complex I with rotenone in a transformed cell line (RGC-5 cells) and to examine the neuroprotective properties of the flavonoids genistein, epigallocatechin gallate (EGCG), epicatechin (EC) and baicalin. Rotenone-induced cell death of RGC-5 cells results in a generation of reactive oxygen species, a breakdown of DNA, the translocation of membrane phosphatidylserine, an up-regulation of haemoxygenase-1 and is unaffected by necrostatin-1 (inhibitor of necroptosis), z-VAD-fmk (pan caspase inhibitor) or NU1025 (PARP inhibitor) but attenuated with SP600125 (JNK inhibitor). Rotenone-induced toxicity of RGC-5 cells also caused an activation of mitogen-activated kinases indicated by an up-regulation and translocation into mitochondria of p-c-Jun, pJNK and pp38. Exposure of RGC-5 cells to rotenone does not affect apoptosis inducing factor or significantly stimulate caspase-3 activity. EGCG and EC both significantly blunt rotenone toxicity of RGC-5 cells at concentrations of 50 μM while genistein and baicalin were without effect. Significantly, genistein is approximately 20 times less efficacious than EGCG (IC 50 2.5 μM) and EC (IC 50 1.5 μM) at inhibiting sodium nitroprusside-induced lipid peroxidation. These studies show that rotenone toxicity of RGC-5 cells is neither necroptosis nor caspasedependent apoptosis but involves the activation of mitogen-activated kinases and is inhibited by a JNK inhibitor, EGCG and EC. Genistein attenuates lipid peroxidation less efficaciously than EC and EGCG and does not affect rotenone toxicity of RGC-5 cells. © Springer Science+Business Media, LLC 2012.

Alfonso J.F.,Instituto Oftalmologico Fernandez Vega | Knorz M.,FreeVis Zentrum Universitatsklinikum | Rincon J.L.,Instituto Oftalmologico IUMO CA | Suarez E.,Instituto Oftalmologico IUMO CA | And 2 more authors.
Journal of Cataract and Refractive Surgery | Year: 2014

Purpose To assess visual outcomes after bilateral implantation of an apodized +3.0 diopter (D) addition power toric diffractive multifocal intraocular lens (IOL). Setting Five study sites in Europe and South America. Design Cohort study. Methods Patients had bilateral implantation of the AcrySof® IQ ReSTOR®+3.0 D toric multifocal IOL. Inclusion criteria were age from 21 to 70 years, need for bilateral cataract extraction or refractive lens exchange, and regular corneal astigmatism from 0.75 to 2.5 D. Six-month evaluations included spherical equivalent (SE), refractive and corneal cylinder, visual acuity at various distances, defocus testing, reading speed, and IOL rotation. Results Forty-four of 49 patients completed the 6-month visit. The mean SE (88 eyes) was 0.09 D ± 0.49 (SD) at 6 months (±1.00 D in 95.2%). The mean refractive cylinder decreased from 1.07 ± 0.71 D to 0.33 ± 0.44 D (≤0.50 D in 78.6% and ≤1.00 D in 92.9%). The mean binocular uncorrected visual acuity was 0.04 ± 0.08 logMAR at preferred near (∼39 cm), 0.07 ± 0.09 logMAR at 40 cm, 0.09 ± 0.11 logMAR at 60 cm, and 0.05 ± 0.10 logMAR at 4 m. The mean corrected reading speed increased from 125.43 ± 33.58 words per minute (wpm) to 132.68 ± 23.69 wpm. The mean IOL rotation was 2.20 ± 4.34 degrees. Conclusion Six months after implantation of the toric multifocal IOL, patients had significantly reduced SE and refractive cylinder, good visual acuity across distances, increased reading speed, and minimal IOL rotation. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. © 2013 ASCRS and ESCRS.

Anitua E.,Biotechnology Institute BTI | Merayo-Lloves J.,Instituto Oftalmologico Fernandez Vega | de La Fuente M.,Biotechnology Institute BTI | Muruzabal F.,Biotechnology Institute BTI | Orive G.,Biotechnology Institute BTI
Investigative Ophthalmology and Visual Science | Year: 2011

PURPOSE. Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGFEndoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied. METHODS. Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated. RESULTS. Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions. CONCLUSIONS. These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Ugarte M.,University of Manchester | Osborne N.N.,Instituto Oftalmologico Fernandez Vega | Osborne N.N.,University of Oxford | Brown L.A.,University of Oxford | Bishop P.N.,University of Manchester
Survey of Ophthalmology | Year: 2013

The essential trace metals iron, zinc, and copper play important roles both in retinal physiology and disease. They are involved in various retinal functions such as phototransduction, the visual cycle, and the process of neurotransmission, being tightly bound to proteins and other molecules to regulate their structure and/or function or as unbound free metal ions. Elevated levels of "free" or loosely bound metal ions can exert toxic effects, and in order to maintain homeostatic levels to protect retinal cells from their toxicity, appropriate mechanisms exist such as metal transporters, chaperones, and the presence of certain storage molecules that tightly bind metals to form nontoxic products. The pathways to maintain homeostatic levels of metals are closely interlinked, with various metabolic pathways directly and/or indirectly affecting their concentrations, compartmentalization, and oxidation/reduction states. Retinal deficiency or excess of these metals can result from systemic depletion and/or overload or from mutations in genes involved in maintaining retinal metal homeostasis, and this is associated with retinal dysfunction and pathology. Iron accumulation in the retina, a characteristic of aging, may be involved in the pathogenesis of retinal diseases such as age-related macular degeneration (AMD). Zinc deficiency is associated with poor dark adaptation. Zinc levels in the human retina and RPE decrease with age in AMD. Copper deficiency is associated with optic neuropathy, but retinal function is maintained. The changes in iron and zinc homeostasis in AMD have led to the speculation that iron chelation and/or zinc supplements may help in its treatment. © 2013 Elsevier Inc.

Coca-Prados M.,Yale University | Coca-Prados M.,Instituto Oftalmologico Fernandez Vega
Journal of Glaucoma | Year: 2014

The blood-aqueous barrier of the eye is composed by tight junctions in the ciliary process nonpigmented epithelium, the endothelial cells in the iris vasculature, and the inner wall endothelium of Schlemm's canal. Tight junctions are gatekeepers of the paracellular transport limiting the selective diffusion of ions and small solutes through the space between neighboring cells. Tight junctions (ie, junctional adhesion molecules, claudins, occludins, zonula occludens, cingulin) are part of the apical junctional complex that also includes the adherens junctions (ie, cadherin-catenin and nectin-afadin complexes) and the gap junctions (ie, connexins). These junctional complexes respond rapidly to pharmacologic agents and physiological changes. Barrier dysfunction can contribute to the pathophysiology of inflammatory ocular diseases in a passive way by the vascular leakage of blood-borne molecules and inflammatory cells into the anterior segment of the eye. Copyright © 2014 by Lippincott Williams & Wilkins.

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