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Endothelial Cell Loss (endothelial + cell_loss)
Selected AbstractsCorneal Graft Rejection Is Accompanied by Apoptosis of the Endothelium and Is Prevented by Gene Therapy With Bcl-xLAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2007R. N Barcia Corneal transplants normally enjoy a high percentage of survival, mainly because the eye is an immune-privileged site. When allograft failure occurs, it is most commonly due to rejection, an immune-mediated reaction that targets the corneal endothelium. While the exact mechanism by which the endothelium is targeted is still unknown, we postulate that corneal endothelial cell loss during allograft failure is mediated by apoptosis. Furthermore, because corneal endothelial cells do not normally regenerate, we hypothesize that suppressing apoptosis in the graft endothelium will promote transplant survival. In a murine model of transplantation, TUNEL staining and confocal microscopy showed apoptosis of the graft endothelium occurring in rejecting corneas as early as 2 weeks posttransplantation. We found that bcl-xL protected cultured corneal endothelial cells from apoptosis and that lentiviral delivery of bcl-xL to the corneal endothelium of donor corneas significantly improved the survival of allografts. These studies suggest a novel approach to improve corneal allograft survival by preventing apoptosis of the endothelium. [source] Time-related Histopathologic Changes in Fresh Frozen Carotid Xenografts in a Pig-to-Goat Implantation ModelARTIFICIAL ORGANS, Issue 10 2009Ji M. Chang Abstract We performed an animal experiment with an emphasis on time-related histopathologic changes to evaluate the clinical feasibility of immunologically nontreated xenogenic vascular grafts. Bilateral porcine carotid arteries were harvested, and then, after short-term freezing at ,70°C, interposed into goats' carotid arteries. An antiplatelet agent was administered orally for 3 months postoperatively. The goats were randomly assigned to five periods of observation (1 week, and 1, 3, 6, and 12 months after implantation); two animals were observed at each of these times. Doppler ultrasonography was performed periodically during the observation period. At predetermined times, grafts were explanted and examined using hematoxylin and eosin, and Masson's trichrome stains. Immunohistochemical evaluations were conducted with T-lymphocyte indicator and von Willebrand factor. Two goats died prematurely, one from respiratory problems related to anesthesia and the other from pneumonia. A total of 16 grafts from the remaining eight animals were evaluated. Grafts were all patent except one at 3 months after transplantation. Histologically, xenogenic arterial grafts showed early endothelial cell loss at 1 week. This was followed by a progressive spread of recipient endothelial cells from the anastomotic site, and re-endothelialization was complete at 1 month. The degree of neointimal and medial thickening increased until 3 months, and then decreased. At 12 months, no additional growth of the intimal or medial layers was observed. Adventitial inflammation became severe at 3 months, but was reduced at 6,12 months. The proportions of CD3-positive T-lymphocytes among inflammatory cell infiltrations were very low. Fresh frozen xenogenic arterial grafts showed acceptable patency throughout the 12-month period and showed no evidence of being unduly influenced by rejection reactions. [source] Serious complications of cosmetic NewColorIris implantationACTA OPHTHALMOLOGICA, Issue 6 2010Justin E. Anderson Acta Ophthalmol. 2010: 88: 700,704 Abstract. Purpose:, This case report describes serious postoperative complications and markedly elevated intraocular pressure (IOP) associated with the NewColorIris cosmetic implant. Methods:, We report an interventional case series of two patients who suffered multiple complications after NewColorIris implantation carried out in Panama. Assessment included visual acuity, photography, endothelial cell count and anterior segment optical coherence tomography (OCT) when possible. Results:, Both patients presented with endothelial cell loss, uveitis, pigment dispersion and elevated IOP. Anterior segment OCT demonstrated irregularities in the position and configuration of the implants within the anterior chamber with resultant areas of implant,iris and implant,endothelial contact. One patient had acute postoperative hyphaema that resolved with anterior chamber tissue plasminogen activator injection. Both patients required explantation OU, one eye has required trabeculectomy, and one eye with bullous keratopathy is being evaluated for Descemet's stripping endothelial keratoplasty. Conclusions:, Implantation of the NewColorIris cosmetic implant can lead to serious complications including hyphaema, uncontrolled IOP, severe endothelial cell loss, bullous keratopathy and anterior uveitis. Explantation may lead to improvement, but permanent damage to the trabecular meshwork and corneal endothelium persists. [source] 3131: Endothelial involvement indicates disease activity in Herpes simplex virus keratitisACTA OPHTHALMOLOGICA, Issue 2010T HILLENAAR Purpose Corneal endotheliitis is a potentially sight-threatening clinical manifestation of herpes simplex virus (HSV) keratitis. Early detection and consequent treatment may prevent development of endothelial decompensation. The goal of this previously published study was to describe the morphological features, frequency, and clinical consequences of endothelial involvement in HSV keratitis as seen by in vivo confocal microscopy (IVCM). Methods We examined both eyes of 250 patients with HSV keratitis by slit-lamp and IVCM. All examinations were assessed for endothelial deviations characteristic of endotheliitis. To determine the specificity, we reviewed our IVCM database for morphologically comparable alterations. This database included 200 healthy volunteers and 1400 patients with various corneal pathologies. The endothelial cell density (ECD) change between the first and last visits of patients with HSV keratitis was evaluated. Results Endotheliitis-specific deviations were detected in 107 of 250 patients with HSV keratitis (43%). Pseudoguttata, enlarged intercellular gaps, infiltration of inflammatory cells into the endothelial layer, loss of defined cell boundaries, spot-like holes, and endothelial denudation disappeared within 3 weeks with appropriate antiviral and anti-inflammatory treatment. Alterations were non-specific for HSV keratitis. Similar alterations were detected in adenoviral, fungal, bacterial, and acanthamoeba keratitis. The HSV affected eyes with endothelial involvement showed a mean ECD decrease of 10.3% per year. Conclusion Endothelial involvement indicates inflammatory activity in HSV keratitis and is associated with irreversible endothelial cell loss. IVCM allows early detection and follow up of endotheliitis-specific alterations. [source] 3133: Planar patch-clamping in human corneal endothelial cells: a new tool for clinical application?ACTA OPHTHALMOLOGICA, Issue 2010S MERGLER Purpose Identification of apoptotic or damaged human corneal endothelial cells (HCECs) is limited to morphological evaluation such as phase contrast microscopy and vital staining. The molecular mechanisms of corneal endothelial cell loss are not fully understood. Special investigations in cellular signalling and ion channel research are necessary to elucidate the mechanisms of corneal cell loss. In this context, it is known that this cell loss is often caused by apoptosis in oxidative stress. Methods Automated planar patch-clamp has become common in drug development and safety programs because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. A particularly successful automated approach is based on planar patch-clamp chips and this is the basis for the technology used here. Routine intracellular or extracellular perfusion opens possibilities for studying the regulation and pharmacology of ion channels. Previously, these studies were available only to highly skilled and dedicated experimenters. Results Notable, definite ion channel activities could be demonstrated by conventional as well as by planar patch-clamp in HCECs for the first time. In particular, temperature-sensing transient receptor potential (TRP)-like non-selective cation channel currents as well as capsaicin-sensitive ion channel currents could be detected. The expression of TRPV1-3 ion channels in HCEC could also be confirmed by RT-PCR, Western blot analysis and fluorescence cell imaging. Conclusion The administration of this novel measuring technology opens new perspectives in the investigation of the physiology of HCEC. The findings may have direct clinical implication (eye banking procedures, keratoplasty). [source] |