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Peter A. Campochiaro - One of the best experts on this subject based on the ideXlab platform.
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Effects of Intraocular Ranibizumab and Bevacizumab in Transgenic Mice Expressing Human Vascular Endothelial Growth Factor
Ophthalmology, 2009Co-Authors: Katsuaki Miki, Daisuke Muramatsu, Akiko Miki, Masato Matsuoka, Sean F. Hackett, Peter A. CampochiaroAbstract:Objective This study compared the effects of Intraocular Injections of ranibizumab (RBZ) and bevacizumab (BVZ) in transgenic mouse models in which human vascular endothelial growth factor (VEGF) causes subretinal neovascularization (NV) or exudative retinal detachment. Design Randomized trials in animal models. Participants Transgenic mice in which the rhodopsin promoter drives expression of human VEGF in photoreceptors ( rho/VEGF mice) and double transgenic mice with doxycycline-inducible expression of human VEGF in photoreceptors ( Tet/opsin/VEGF mice). Methods Rho/VEGF mice received Intraocular Injections of RBZ, BVZ, or vehicle, and after various time periods the area of subretinal NV was measured. Tet/opsin/VEGF mice were given an Intraocular Injection of RBZ, BVZ, or vehicle, and after 5 days of doxycycline treatment the presence or absence of retinal detachment was determined. Main Outcome Measures Area of subretinal NV per retina in rho/VEGF mice and the occurrence of retinal detachment in Tet/opsin/VEGF mice. Results In rho/VEGF mice, Intraocular Injections of RBZ or BVZ strongly suppressed subretinal NV, but the duration of effect was greater for BVZ. Three Injections of 10 μg of BVZ over the course of 2 weeks not only suppressed subretinal NV in the injected eye but also caused significant suppression in the fellow eye, indicating a systemic effect. In doxycycline-treated Tet/opsin/VEGF mice, Intraocular Injection of 10 μg of BVZ significantly reduced the incidence of exudative retinal detachment compared with Injection of 10 μg of RBZ. Injection of 25 μg of BVZ reduced the incidence of retinal detachment in both eyes. Conclusions Intraocular Injections of RBZ and BVZ had similar efficacy in rho/VEGF mice, but the duration of effect was greater for BVZ. In Tet/opsin/VEGF mice, in which expression levels of human VEGF are very high and the phenotype is severe, BVZ showed greater efficacy than RBZ. In both models, higher doses or repeated Injections of BVZ, but not RBZ, resulted in a systemic effect. These data suggest that BVZ is not inferior to RBZ for treatment of subretinal NV in mice and is superior in a severe model. The systemic effects of BVZ after Intraocular Injection deserve further study and consideration of their potential consequences. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.
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Blockade of sphingosine-1-phosphate reduces macrophage influx and retinal and choroidal neovascularization.
Journal of Cellular Physiology, 2008Co-Authors: Bing Xie, Jikui Shen, Aling Dong, Aymen Rashid, Glenn Stoller, Peter A. CampochiaroAbstract:Sphingosine-1-phosphate (S1P) is a bioactive lipid molecule that stimulates endothelial cell migration, proliferation, and survival in vitro, and tumor angiogenesis in vivo. In this study, we used a humanized monoclonal antibody (sonepcizumab) that selectively binds S1P to investigate its role in retinal and choroidal neovascularization (NV). Intraocular Injection of sonepcizumab significantly reduced macrophage influx into ischemic retina and strongly suppressed retinal NV in mice with oxygen-induced ischemic retinopathy. In mice with laser-induced rupture sites in Bruch's membrane, Intraocular Injection of sonepcizumab significantly reduced the area of choroidal NV and concomitantly reduced fluorescein leakage from the remaining choroidal NV. Four weeks after Intraocular Injection of up to 1.8 mg of the sonepcizumab in non-human primates, electroretinograms and fluorescein angiograms were normal, and light microscopy of ocular sections showed no evidence of structural damage. These data show for the first time that S1P stimulates both choroidal and retinal NV and suggest that sonepcizumab could be considered for evaluation in patients with choroidal or retinal NV. J. Cell. Physiol. 218: 192–198, 2009. © 2008 Wiley-Liss, Inc.
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Intraocular Injection of an aptamer that binds pdgf b a potential treatment for proliferative retinopathies
Journal of Cellular Physiology, 2006Co-Authors: Hideo Akiyama, Sean F. Hackett, Shu Kachi, Raquel Lima E Silva, Naoyasu Umeda, Dilara Mccauley, Thomas G Mccauley, Anna J Zoltoski, David M Epstein, Peter A. CampochiaroAbstract:Platelet-derived growth factor-B (PDGF-B) has been implicated in the pathogenesis of proliferative retinopathies and other scarring disorders in the eye. In this study, we sought to test the therapeutic potential of an aptamer that selectively binds PDGF-B, ARC126, and its PEGylated derivative, ARC127. Both ARC126 and ARC127 blocked PDGF-B-induced proliferation of cultured fibroblasts with an IC50 of 4 nM. Pharmacokinetic studies in rabbits showed similar peak vitreous concentrations of approximately 110 µM after intravitreous Injection of 1 mg of either ARC126 or ARC127, but the terminal half-life was longer for ARC127 (98 versus 43 h). Efficacy was tested in rho/PDGF-B transgenic mice that express PDGF-B in photoreceptors and develop severe proliferative retinopathy resulting in retinal detachment. Compared to eyes injected with 20 µg of scrambled aptamer in which five of six developed detachments (three total and two partial), eyes injected with ARC126 (no detachment in five of six and one partial detachment), or ARC127 (no detachment in six of six) had significantly fewer retinal detachments. They also showed a significant reduction in epiretinal membrane formation. These data demonstrate that a single intravitreous Injection of an aptamer that specifically binds PDGF-B is able to significantly reduce epiretinal membrane formation and retinal detachment in rho/PDGF-B mice. These striking effects in an aggressive model of proliferative retinopathy suggest that ARC126 and ARC127 should be considered for treatment of diseases in which PDGF-B has been implicated, including ischemic retinopathies such as proliferative diabetic retinopathy, proliferative vitreoretinopathy (PVR), and choroidal neovascularization. J. Cell. Physiol. 207: 407–412, 2006. © 2006 Wiley-Liss, Inc.
Jay M Stewart - One of the best experts on this subject based on the ideXlab platform.
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delayed acute granulomatous anterior uveitis after inadvertent Intraocular Injection of tattoo ink from a scleral tattoo procedure
Ocular Immunology and Inflammation, 2020Co-Authors: Neel Pasricha, Greg Bever, Gerami Seitzman, Jay M StewartAbstract:To improve awareness of delayed onset uveitis in patients with a history of Intraocular tattoo ink Injection. A 47-year-old man underwent a scleral tattoo procedure during which there was inadverte...
Arnd Heiligenhaus - One of the best experts on this subject based on the ideXlab platform.
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intraoperative Intraocular triamcinolone Injection prophylaxis for post cataract surgery fibrin formation in uveitis associated with juvenile idiopathic arthritis
Journal of Cataract and Refractive Surgery, 2006Co-Authors: Carsten Heinz, Beatrix Zurekimhoff, Arnd HeiligenhausAbstract:Purpose To assess the efficacy of a single intraoperative Intraocular Injection of triamcinolone acetonide during cataract surgery to prevent postoperative fibrin formation in patients with iridocyclitis associated with juvenile idiopathic arthritis. Setting Department of Ophthalmology, St. Franziskus Hospital, Muenster, Germany. Methods The charts of 22 patients (16 girls and 6 boys) with juvenile idiopathic arthritis and chronic iridocyclitis having lensectomy and anterior vitrectomy were retrospectively reviewed. In 12 patients (14 eyes), triamcinolone acetonide 4 mg was injected into the anterior chamber at the end of the surgery (triamcinolone group). Another 10 patients (13 eyes) received an intraoperative intravenous Injection of methylprednisolone and postoperative oral prednisolone (systemic treatment group). No Intraocular lenses were implanted. Postoperatively, prednisolone acetate 1% eyedrops were given. The main problems included Intraocular inflammation, the need for additional systemic corticosteroids, and Intraocular pressure (IOP) elevation. Results The mean patient age was 10.6 years ± 3.1 (SD) in the triamcinolone group and 7.4 ± 2.7 years in the systemic treatment group. The mean follow-up was 9.9 ± 3.6 months and 10.9 ± 1.2 months, respectively. All patients were taking systemic immunosuppression before surgery, and the medication was continued postoperatively. Fibrin formation was not seen after surgery in the triamcinolone group but occurred in 5 patients in the systemic treatment group (P = .02). Additional systemic corticosteroids were not required in the triamcinolone group. All patients had visual acuity improvement. No increase in IOP was noted after the triamcinolone acetate Injections. Conclusions Intraoperative Intraocular Injection of 4 mg of triamcinolone acetonide may be more effective than intraoperative intravenous methylprednisolone and additional postoperative short-term oral prednisolone in preventing postoperative fibrin formation after cataract surgery in patients with juvenile idiopathic arthritis and iridocyclitis.
Neel Pasricha - One of the best experts on this subject based on the ideXlab platform.
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delayed acute granulomatous anterior uveitis after inadvertent Intraocular Injection of tattoo ink from a scleral tattoo procedure
Ocular Immunology and Inflammation, 2020Co-Authors: Neel Pasricha, Greg Bever, Gerami Seitzman, Jay M StewartAbstract:To improve awareness of delayed onset uveitis in patients with a history of Intraocular tattoo ink Injection. A 47-year-old man underwent a scleral tattoo procedure during which there was inadverte...
Alexander W. Pfaff - One of the best experts on this subject based on the ideXlab platform.
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Early expression and subsequent loss of retinal cytokine production following Intraocular infection with the RH strain of T. gondii.
2019Co-Authors: Elise Rochet, Nicolas Argy, Valentin Greigert, Julie Brunet, Marcela Sabou, Luc Marcellin, Alejandra De-la-torre, Arnaud Sauer, Ermanno Candolfi, Alexander W. PfaffAbstract:C57BL/6 mice were infected by Intraocular Injection of 2000 T. gondii tachyzoites of different strains. Cytokine producing cells were localized by immunofluorescence on retinal cryosections (arrows).
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Retinal cytokine expression depends both on background strain and on the ROP16 allele.
2019Co-Authors: Elise Rochet, Nicolas Argy, Valentin Greigert, Julie Brunet, Marcela Sabou, Luc Marcellin, Alejandra De-la-torre, Arnaud Sauer, Ermanno Candolfi, Alexander W. PfaffAbstract:C57BL/6 mice were infected by Intraocular Injection of 2000 T. gondii tachyzoites of different strains. Retinal expression of Th1 and inflammatory cytokines was detected by immunoflurorescence 7 days after infection (arrows). GCL ganglion cell layer; INR inner nuclear layer; ONL outer nuclear layer.
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Ocular parasite load depends both on parental strain and ROP16 allele.
2019Co-Authors: Elise Rochet, Nicolas Argy, Valentin Greigert, Julie Brunet, Marcela Sabou, Luc Marcellin, Alejandra De-la-torre, Arnaud Sauer, Ermanno Candolfi, Alexander W. PfaffAbstract:C57BL/6 mice were infected by Intraocular Injection of 2000 T. gondii tachyzoites of different strains. The parasite load was determined by quantitative PCR on DNA extracted from whole eyes. Values shown are means ± SD of three independent experiments on pools of four mice (eight eyes). ☠ All mice infected with RH and RHΔROP16 strains died before 14 dpi. ** P < 0.01; *** P < 0.001.
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Retinal pathology following Intraocular infection with different strains of T. gondii does not correlate with parasite load.
2019Co-Authors: Elise Rochet, Nicolas Argy, Valentin Greigert, Julie Brunet, Marcela Sabou, Luc Marcellin, Alejandra De-la-torre, Arnaud Sauer, Ermanno Candolfi, Alexander W. PfaffAbstract:C57BL/6 mice were infected by Intraocular Injection of 2000 T. gondii tachyzoites of different strains. Hematoxylin-eosin staining of retina sections. GCL ganglion cell layer; IPL inner plexiform layer; INR inner nuclear layer; OPL outer plexiform layer; ONL outer nuclear layer; Pho photoreceptor layer. ☠ All mice infected with RH and RHΔROP16 strains died before day 14. The arrows show the characteristic pathological features described in the text.