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Sample records for intravitreal ngf administration

  1. Fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone administration

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    Ryan Rush

    2012-01-01

    Full Text Available We report two cases of fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone acetonide (IVTA administration. Case 1: A 42-year-old female received IVTA for presumed non-infectious panuveitis. Within 2 months, she developed diffuse macular retinochoroiditis with optic disc edema. Upon starting anti-toxoplasmic therapy (ATT, her intraocular inflammation resolved with catastrophic damage to the disc and macula. Case 2: A 30-year-old male received IVTA for presumed reactivation of previously scarred toxoplasmic retinochoroiditis. Despite simultaneous ATT, within 6 weeks, he developed extensive, multifocal macular retinochoroiditis. He continued to require ATT for 18 months and later underwent vitrectomy with silicone oil placement for severe epiretinal proliferation. Aqueous tap polymerase chain reactions were found positive for Toxoplasma gondii in both cases. In conclusion, IVTA administration can lead to fulminant toxoplasmic retinochoroiditis even when used with appropriate ATT. Extreme caution should be exercised while administering depot corticosteroids in eyes with panuveitis of unknown origin.

  2. Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration

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    Valeria Colafrancesco

    2011-01-01

    Full Text Available The aim of this study was to investigate the effect of nerve growth factor (NGF administration on retinal ganglion cells (RGCs in experimentally induced glaucoma (GL and diabetic retinopathy (DR. GL was induced in adult rats by injection of hypertonic saline into the episcleral vein of the eye and diabetes (DT was induced by administration of streptozoticin. Control and experimental rats were treated daily with either ocular application of NGF or vehicle solution. We found that both animal models present a progressive degeneration of RGCs and changing NGF and VEGF levels in the retina and optic nerve. We then proved that NGF eye drop administration exerts a protective effect on these models of retinal degeneration. In brief, our findings indicate that NGF can play a protective role against RGC degeneration occurring in GL and DR and suggest that ocular NGF administration might be an effective pharmacological approach.

  3. Liposomal Formulation of Bevasizuamb for Intravitreal Administration: Increased Half-Life, Decreased Side Effects

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    Siamak Zarei Ghanavati

    2008-05-01

    Full Text Available Intravitreal injection is the common method for treatment of the posterior segment eye diseases. The advantage of intravitreal injection is achieving the desired concentration of drug inside the eye and reduction of drug side effects. Unfortunately, repeated intravitreal injections can cause several ocular complications including; vitreous hemorrhage, endophthalmitis, retinal detachment and cataract. For this reason, it seems the usage of sustained release drug delivery systems is helpful. Bevacizumab (Avastin®, antivascular endothelial growth factor (VEGF monoclonal antibody, is used for the treatment of different ocular diseases such as neovascular age-related macular degeneration, neovascular glaucoma, diabetic retinopathy, retinal vein occlusions, etc. For reduction of drug side effects and improvement of drug half-life after intravitreal administration, we suggest preparation of liposomal bevacizumab as novel drug delivery system and comparison of this new formulation with conventional formulation in the market.

  4. Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

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    Moisseiev, Elad; Waisbourd, Michael; Ben-Artsi, Elad; Levinger, Eliya; Barak, Adiel; Daniels, Tad; Csaky, Karl; Loewenstein, Anat; Barequet, Irina S.

    2013-01-01

    Background Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data. Methods Tw...

  5. Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells

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    Álcio Coutinho de Paula

    2015-04-01

    Full Text Available Purpose: To assess the cytotoxicity and genotoxicity of intravitreal adalimumab treatment in an animal experimental model using cytological and molecular techniques. Methods: Eighteen rabbits were randomly assigned to three groups: control, adalimumab treatment, and placebo. Cytotoxicity on retinal cells was evaluated using flow cytometry assays to determine the level of apoptosis and necrosis. Genotoxicity was evaluated by comet assays to assess DNA damage, and quantitative real-time polymerase chain reaction (qPCR was used to evaluate expression of apoptosis-inducing caspases (8 and 3. Results: No cytotoxicity or genotoxicity was observed in any of the two treatment groups (adalimumab and placebo following intravitreal administration compared with the control group. Flow cytometry analysis revealed that more than 90% of the cells were viable, and only a low proportion of retinal cells presented apoptotic (~10% or necrotic (<1% activity across all groups. Molecular damage was also low with a maximum of 6.4% DNA degradation observed in the comet assays. In addition, no increase in gene expression of apoptosis-inducing caspases was observed on retinal cells by qPCR in both the adalimumab and placebo groups compared with the control group. Conclusion: The use of adalimumab resulted in no detectable cytotoxicity or genotoxicity on retinal cells for up to 60 days upon administration. These results therefore indicate that adalimumab may be a safe option for intravitreal application to treat ocular inflammatory diseases in which TNF-α is involved.

  6. Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

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    Dimitrios Brouzas

    2009-08-01

    Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

  7. The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement.

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    Kokona, Despina; Charalampopoulos, Ioannis; Pediaditakis, Iosif; Gravanis, Achille; Thermos, Kyriaki

    2012-04-01

    The aim of the present study was to investigate the neuroprotective properties of the endogenous neurosteroid dehydroepiandrosterone (DHEA) in an in vivo model of retinal excitotoxicity, and the involvement of Nerve Growth Factor (NGF) in its actions. Adult Sprague-Dawley rats (250-300 g) received intravitreally (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA; 42 nmol/eye) alone or in combination with DHEA (10(-8), 10(-7), 10(-6) M), or PBS (50 mM, control group). To examine the involvement of NGF and its TrkA receptor in the pharmacological effects of DHEA, animals received AMPA and NGF (60 pg/eye) in the absence or presence of a TrkA receptor inhibitor (Calbiochem 648450, 10(-6) M) or AMPA, DHEA (10(-6) M) and TrkA receptor inhibitor (10(-6), 10(-5) M). Immunohistochemistry studies [choline acetyltransferase (ChAT), brain nitric oxide synthetase (bNOS), calbindin, and TUNEL] and fluorescence-activated cell sorting (FACS) were used to examine retinal cell loss and protection. TrkA receptor immunoreactivity (-IR) and colocalization studies with relevant markers were also performed. AMPA (42 nmol) treatment resulted in a loss of bNOS, ChAT and calbindin immunoreactivities 24 h after its administration. DHEA, administered intravitreally, protected the retina from excitotoxicity in a dose-dependent manner. This effect was mimicked by NGF, and reversed by the NGF TrkA receptor inhibitor. The TrkA receptor is expressed in ganglion cells of rat retina. TUNEL staining and FACS analysis substantiated the neuroprotective actions of DHEA. These results demonstrate for the first time that the neurosteroid DHEA, administered intravitreally, protects the retina from AMPA excitotoxicity. An NGF TrkA receptor mechanism appears to be involved in this neuroprotection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. NGF and therapeutic prospective: what have we learned from the NGF transgenic models?

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    Luigi Aloe

    2015-03-01

    Full Text Available It has been shown that topical nerve growth factor (NGF administration induces healing action on human cutaneous, corneal and pressure ulcers, glaucoma, maculopathy and retinitis pigmentosa suggesting a therapeutic potential of NGF in human ophthalmology and cutaneous ulcers. A similar therapeutic suggestion has emerged for the NGF gene therapy of Alzheimer's disease and ischemic heart injury. Moreover, over the last few years, the role and biological properties of NGF have also been investigated with transgenic mice over-expressing and down-expressing NGF. However, the results obtained with these transgenic mice seem suitable to confirm and/or support the evidence obtained with exogenous administration of NGF regarding the suggested clinical potentiality of NGF. The aim of the present brief review is to report and comment on these two different findings of NGF's healing properties.

  9. The effect of intravitreal administration of bevacizumab on macular edema and visual acuity in age-related macular degeneration with subfoveolar choroidal neovascularisation

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    Ristić Dragana

    2013-01-01

    Full Text Available Background/Aim. Age-related macular degeneration (AMD is a leading cause of the loss of central visual acuity in population older than 70 years. We can distinguish wet and dry form of AMD. The aim of the study was to present our early results in treatment of the wet (neovascular form of AMD with intravitreal administration of bevacizumab. Methods. The study included 39 patients. Each patient underwent a complete ophthalmological examination, fluorescein angiography (FA and optical coherence tomography (OCT. All the patients received 1.25 mg of intravitreal bevacizumab (0.05 mL of commercial phial of Avastin®. The total of three doses was given with a one-month interval between doses. Results. Among 39 patients, 24 were women and 15 men. The average best corrected visual acuity (BCVA was improved from 0.09 before the therapy to 0.24 after the administration of all the three doses of bevacizumab (p < 0.001. The average central macular thickness (CMT measured by OCT was improved from 474 μm in the beginning to 341 μm after the administration of all the three doses of the drug (p < 0.001. There were no side effects. Conclusions. Our short-term experience indicates that intravitreal administration of three doses of bevacizumab in one-month intervals between the doses leads to a significant reduction of macular edema and improvement of BCVA in patients with neovascular AMD.

  10. The effect of repeated administrations of llama ovulation-inducing factor (OIF/NGF) during the peri-ovulatory period on corpus luteum development and function in llamas.

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    Fernández, A; Ulloa-Leal, C; Silva, M; Norambuena, C; Adams, G P; Guerra, M; Ratto, M H

    2014-10-01

    The objective of the study was to test the hypothesis that repeated administrations of OIF/NGF during the peri-ovulatory period (pre-ovulatory, ovulatory, early post-ovulatory), will enhance the luteotrophic effect in llamas. Female llamas were examined daily by transrectal ultrasonography in B- and Doppler-mode using a scanner equipped with a 7.5-MHz linear-array transducer to monitor ovarian follicle and luteal dynamics. When a growing follicle ≥7mm was detected, llamas were assigned randomly to one of the three groups and given 1mg of purified OIF/NGF im (intramuscular) (a) pre-ovulation (single dose; n=12), (b) pre-ovulation and at the time of ovulation (2 doses, n=10), or (c) pre-ovulation, at the time of ovulation, and 24h after ovulation (3 doses, n=10). The pre-ovulatory follicle diameter at the time of treatment, ovulation rate and the first day of CL detection did not differ (P=0.3) among groups. However, maximum CL diameter was greatest (P=0.003) in llamas in the 2-dose group, and smallest in the 3-dose group. Accordingly, the 2 dose-group had the largest day-to-day profile for CL diameter (Pllama seminal plasma is luteotrophic and the effect on CL size and function is affected by the number and timing of treatments during the peri-ovulatory period.

  11. High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

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    Akiyama, Hiroki; Takase, Hiroshi; Kubo, Fumito; Miki, Tohru; Yamamoto, Masahide; Tomita, Makoto; Mochizuki, Manabu; Miura, Osamu; Arai, Ayako

    2016-10-01

    In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m(2) ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).

  12. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease.

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    Mei Li

    Full Text Available Huntington disease (HD is an inherited neurodegenerative disease that affects multiple brain regions. It is caused by an expanded polyglutamine tract in huntingtin (Htt. The development of therapies for HD and other neurodegenerative diseases has been hampered by multiple factors, including the lack of clear therapeutic targets, and the cost and complexity of testing lead compounds in vivo. The R6/2 HD mouse model is widely used for pre-clinical trials because of its progressive and robust neural dysfunction, which includes retinal degeneration. Profilin-1 is a Htt binding protein that inhibits Htt aggregation. Its binding to Htt is regulated by the rho-associated kinase (ROCK, which phosphorylates profilin at Ser-137. ROCK is thus a therapeutic target in HD. The ROCK inhibitor Y-27632 reduces Htt toxicity in fly and mouse models. Here we characterized the progressive retinopathy of R6/2 mice between 6-19 weeks of age to determine an optimal treatment window. We then tested a clinically approved ROCK inhibitor, HA-1077, administered intravitreally via liposome-mediated drug delivery. HA-1077 increased photopic and flicker ERG response amplitudes in R6/2 mice, but not in wild-type littermate controls. By targeting ROCK with a new inhibitor, and testing its effects in a novel in vivo model, these results validate the in vivo efficacy of a therapeutic candidate, and establish the feasibility of using the retina as a readout for CNS function in models of neurodegenerative disease.

  13. Effect of Purified Murine NGF on Isolated Photoreceptors of a Rodent Developing Retinitis Pigmentosa

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    Rocco, Maria Luisa; Balzamino, Bijorn Omar; Petrocchi Passeri, Pamela; Micera, Alessandra; Aloe, Luigi

    2015-01-01

    A number of different studies have shown that neurotrophins, including nerve growth factor (NGF) support the survival of retinal ganglion neurons during a variety if insults. Recently, we have reported that that eye NGF administration can protect also photoreceptor degeneration in a mice and rat with inherited retinitis pigmentosa. However, the evidence that NGF acts directly on photoreceptors and that other retinal cells mediate the NGF effect could not be excluded. In the present study we have isolated retinal cells from rats with inherited retinitis pigmentosa (RP) during the post-natal stage of photoreceptor degenerative. In presence of NGF, these cells are characterized by enhanced expression of NGF-receptors and rhodopsin, the specific marker of photoreceptor and better cell survival, as well as neuritis outgrowth. Together these observations support the hypothesis that NGF that NGF acts directly on photoreceptors survival and prevents photoreceptor degeneration as previously suggested by in vivo studies. PMID:25897972

  14. NGF-evoked sensitization of muscle fascia nociceptors in humans.

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    Deising, Saskia; Weinkauf, Benjamin; Blunk, James; Obreja, Otilia; Schmelz, Martin; Rukwied, Roman

    2012-08-01

    Nerve growth factor (NGF) induces local hyperalgesia for a few days after intramuscular injection, but longer-lasting muscle pain upon systemic administration. As the muscle fascia is densely innervated by free nerve endings, we hypothesized a lasting sensitization of fascia nociceptors by NGF. We administered 1 μg NGF (dissolved in 100 μL saline) ultrasound-guided to the fascia of the Musculus erector spinae muscle at the lumbar level of 14 male volunteers and assessed hypersensitivity after 6 hours, and 1, 3, 7, 14, and 21 days. Pain upon mechanical stimuli (constant pressure and dynamic impact), upon exercise and electrically induced M. erector spinae contraction, and upon injection of 100 μL phosphate buffer pH4 (at day 7 and 14 only) to the fascia of both NGF- and saline-treated muscles, was investigated. Injections into the muscle fascia did not cause acute pain. Local heat pain thresholds were unchanged following NGF and saline (control) administration. NGF evoked a lasting (days 1-7) and significant reduction of pressure pain, pressure thresholds, exercise-evoked muscle pain, and hyperalgesia to impact stimuli (12 m/s). Pain upon injected protons was significantly elevated (Pfascia to mechanical and chemical stimuli lasting for up to 2 weeks. As nociceptors in the fascia appear to be particularly prone to sensitization, they may contribute to acute or chronic muscle pain. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. NGF and proNGF reciprocal interference in immunoassays : open questions, criticalities and ways forward

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    Francesca Malerba

    2016-08-01

    Full Text Available The homeostasis between mature neurotrophin NGF and its precursor proNGF is thought to be crucial in physiology and in pathological states. Therefore, the measurement of the relative amounts of NGF and proNGF could serve as a footprint for the identification of disease states, for diagnostic purposes. Since NGF is part of proNGF, their selective identification with anti-NGF antibodies is not straightforward. Currently, many immunoassays for NGF measurement are available, while the proNGF assays are few and not validated by published information.The question arises, as to whether the commercially available assays are able to distinguish between the two forms. Also, since in biological samples the two forms coexist, are the measurements of one species affected by the presence of the other? We describe experiments addressing these questions. For the first time, NGF and proNGF were measured together and tested in different immunoassays. Unexpectedly, NGF and proNGF were found to reciprocally interfere with the experimental outcome. The interference also calls into question the widely used NGF ELISA methods, applied to biological samples where NGF and proNGF coexist. Therefore, an immunoassay, able to distinguish between the two forms is needed. We propose possible ways forward, towards the development of a selective assay. In particular, the use of the well validated anti-NGF αD11 antibody in an alphaLISA assay with optimized incubation times would be a solution to avoid the interference in the measurement of a mixed sample containing NGF and proNGF. Furthermore, we explored the possibility of measuring proNGF in a biological sample. But the available commercial kit for the detection of proNGF does not allow the measurement of proNGF in mouse brain tissues.Therefore, we validated an SPR approach for the measurement of proNGF in a biological sample.Our experiments help in understanding the technical limits in the measurement of the NGF/proNGF ratio

  16. Diabetes and overexpression of proNGF cause retinal neurodegeneration via activation of RhoA pathway.

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    Mohammed M H Al-Gayyar

    Full Text Available Our previous studies showed positive correlation between accumulation of proNGF, activation of RhoA and neuronal death in diabetic models. Here, we examined the neuroprotective effects of selective inhibition of RhoA kinase in the diabetic rat retina and in a model that stably overexpressed the cleavage-resistance proNGF plasmid in the retina. Male Sprague-Dawley rats were rendered diabetic using streptozotocin or stably express cleavage-resistant proNGF plasmid. The neuroprotective effects of the intravitreal injection of RhoA kinase inhibitor Y27632 were examined in vivo. Effects of proNGF were examined in freshly isolated primary retinal ganglion cell (RGC cultures and RGC-5 cell line. Retinal neurodegeneration was assessed by counting TUNEL-positive and Brn-3a positive retinal ganglion cells. Expression of proNGF, p75(NTR, cleaved-PARP, caspase-3 and p38MAPK/JNK were examined by Western-blot. Activation of RhoA was assessed by pull-down assay and G-LISA. Diabetes and overexpression of proNGF resulted in retinal neurodegeneration as indicated by 9- and 6-fold increase in TUNEL-positive cells, respectively. In vitro, proNGF induced 5-fold cell death in RGC-5 cell line, and it induced >10-fold cell death in primary RGC cultures. These effects were associated with significant upregulation of p75(NTR and activation of RhoA. While proNGF induced TNF-α expression in vivo, it selectively activated RhoA in primary RGC cultures and RGC-5 cell line. Inhibiting RhoA kinase with Y27632 significantly reduced diabetes- and proNGF-induced activation of proapoptotic p38MAPK/JNK, expression of cleaved-PARP and caspase-3 and prevented retinal neurodegeneration in vivo and in vitro. Taken together, these results provide compelling evidence for a causal role of proNGF in diabetes-induced retinal neurodegeneration through enhancing p75(NTR expression and direct activation of RhoA and p38MAPK/JNK apoptotic pathways.

  17. Diabetes and Overexpression of proNGF Cause Retinal Neurodegeneration via Activation of RhoA Pathway

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    Matragoon, Suraporn; Abdelsaid, Mohammed A.; El-Azab, Mona F.; Shanab, Ahmed Y.; Ha, Yonju; Smith, Sylvia B.; Bollinger, Kathryn E.; El-Remessy, Azza B.

    2013-01-01

    Our previous studies showed positive correlation between accumulation of proNGF, activation of RhoA and neuronal death in diabetic models. Here, we examined the neuroprotective effects of selective inhibition of RhoA kinase in the diabetic rat retina and in a model that stably overexpressed the cleavage-resistance proNGF plasmid in the retina. Male Sprague-Dawley rats were rendered diabetic using streptozotosin or stably express cleavage-resistant proNGF plasmid. The neuroprotective effects of the intravitreal injection of RhoA kinase inhibitor Y27632 were examined in vivo. Effects of proNGF were examined in freshly isolated primary retinal ganglion cell (RGC) cultures and RGC-5 cell line. Retinal neurodegeneration was assessed by counting TUNEL-positive and Brn-3a positive retinal ganglion cells. Expression of proNGF, p75NTR, cleaved-PARP, caspase-3 and p38MAPK/JNK were examined by Western-blot. Activation of RhoA was assessed by pull-down assay and G-LISA. Diabetes and overexpression of proNGF resulted in retinal neurodegeneration as indicated by 9- and 6-fold increase in TUNEL-positive cells, respectively. In vitro, proNGF induced 5-fold cell death in RGC-5 cell line, and it induced >10-fold cell death in primary RGC cultures. These effects were associated with significant upregulation of p75NTR and activation of RhoA. While proNGF induced TNF-α expression in vivo, it selectively activated RhoA in primary RGC cultures and RGC-5 cell line. Inhibiting RhoA kinase with Y27632 significantly reduced diabetes- and proNGF-induced activation of proapoptotic p38MAPK/JNK, expression of cleaved-PARP and caspase-3 and prevented retinal neurodegeneration in vivo and in vitro. Taken together, these results provide compelling evidence for a causal role of proNGF in diabetes-induced retinal neurodegeneration through enhancing p75NTR expression and direct activation of RhoA and p38MAPK/JNK apoptotic pathways. PMID:23365678

  18. [The results of intravitreal bevacizumab in high myopic subretinal neovascularisation].

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    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To asses the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization secondary to pathologic myopia; To asses the safety and results stability; Prospective, interventional case study of 18 eyes with choroidal neovascularization secondary to pathologic myopia treated with 1.25 mg. intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. Mean age of patients in the study was 43.86%--6.32 years (ranging 24-62 years). The mean number of intravitreal injections was 2.62%--0.53 (ranging between 1 - 4 injections). Mean visual acuity improved in all cases. An increase of more than 15 letters was noted in 44.44.% of the cases. OCT confirmed a reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the choroidal neovascularization reappeared in 5 cases (27.77%) requiring additional treatment. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the choroidal neovascularization secondary to pathologic myopia. More than 40% of the cases regained at least 3 lines in ETDRS chart but a recurrence was noted in 27.77% of the cases at 6 months.

  19. The effect of intravitreal bevacizumab and ranibizumab on macular edema of the contralateral eye: A comparative study of two anti-VEGFs

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    Berker Bakbak

    2016-01-01

    Conclusions: In contrast to ranibizumab, the intravitreal administration of bevacizumab resulted in a statistically significant decrease in macular thickness in the untreated eye in patients with bilateral DME.

  20. Expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 in cocultures of dissociated DRG neurons and skeletal muscle cells in administration of NGF or NT-3.

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    Zhang, Weiwei; Li, Hao; Xing, Ziying; Yuan, Hongtu; Kindy, Mark S; Li, Zhenzhong

    2012-07-05

    Both neurotrophins (NTs) and target skeletal muscle (SKM) cells are essential for the maintenance of the function of neurons and nerve-muscle communication. However, much less is known about the association of target SKM cells with distinct NTs on the expression of mRNAs for preprotachykinin (PPT), calcitonin-gene related peptide (CGRP), neurofilament 200 (NF-200), and microtubule associated protein 2 (MAP-2) in dorsal root ganglion (DRG) sensory neurons. In the present study, a neuromuscular coculture model of dissociated dorsal root ganglion (DRG) neurons and SKM cells was established. The morphology of DRG neurons and SKM cells in coculture was observed with an inverted phase contrast microscope. The effects of nerve growth factor (NGF) or neurotrophin-3 (NT-3) on the expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 was analyzed by real time-PCR assay. The morphology of DRG neuronal cell bodies and SKM cells in neuromuscular coculture at different conditions was similar. The neurons presented evidence of dense neurite outgrowth in the presence of distinct NTs in neuromuscular cocultures. NGF and NT-3 increased mRNA levels of PPT, CGRP, and NF-200, but not MAP-2, in neuromuscular cocultures. These results offer new clues towards a better understanding of the association of target SKM cells with distinct NTs on the expression of mRNAs for PPT, CGRP, NF-200 and MAP-2, and implicate the association of target SKM cells and NTs with DRG sensory neuronal phenotypes.

  1. Expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 in cocultures of dissociated DRG neurons and skeletal muscle cells in administration of NGF or NT-3

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    Weiwei Zhang

    2012-07-01

    Full Text Available Both neurotrophins (NTs and target skeletal muscle (SKM cells are essential for the maintenance of the function of neurons and nerve-muscle communication. However, much less is known about the association of target SKM cells with distinct NTs on the expression of mRNAs for preprotachykinin (PPT, calcitonin-gene related peptide (CGRP, neurofilament 200 (NF-200, and microtubule associated protein 2 (MAP-2 in dorsal root ganglion (DRG sensory neurons. In the present study, a neuromuscular coculture model of dissociated dorsal root ganglion (DRG neurons and SKM cells was established. The morphology of DRG neurons and SKM cells in coculture was observed with an inverted phase contrast microscope. The effects of nerve growth factor (NGF or neurotrophin-3 (NT-3 on the expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 was analyzed by real time-PCR assay. The morphology of DRG neuronal cell bodies and SKM cells in neuromuscular coculture at different conditions was similar. The neurons presented evidence of dense neurite outgrowth in the presence of distinct NTs in neuromuscular cocultures. NGF and NT-3 increased mRNA levels of PPT, CGRP, and NF-200, but not MAP-2, in neuromuscular cocultures. These results offer new clues towards a better understanding of the association of target SKM cells with distinct NTs on the expression of mRNAs for PPT, CGRP, NF-200 and MAP-2, and implicate the association of target SKM cells and NTs with DRG sensory neuronal phenotypes.

  2. Functional Characterization of Human ProNGF and NGF Mutants: Identification of NGF P61SR100E as a "Painless" Lead Investigational Candidate for Therapeutic Applications.

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    Francesca Malerba

    Full Text Available Nerve Growth Factor (NGF holds a great therapeutic promise for Alzheimer's disease, diabetic neuropathies, ophthalmic diseases, dermatological ulcers. However, the necessity for systemic delivery has hampered the clinical applications of NGF due to its potent pro-nociceptive action. A "painless" human NGF (hNGF R100E mutant has been engineered. It has equal neurotrophic potency to hNGF but a lower nociceptive activity. We previously described and characterized the neurotrophic and nociceptive properties also of the hNGF P61S and P61SR100E mutants, selectively detectable against wild type hNGF. However, the reduced pain-sensitizing potency of the "painless" hNGF mutants has not been quantified.Aiming at the therapeutic application of the "painless" hNGF mutants, we report on the comparative functional characterization of the precursor and mature forms of the mutants hNGF R100E and hNGF P61SR100E as therapeutic candidates, also in comparison to wild type hNGF and to hNGF P61S. The mutants were assessed by a number of biochemical, biophysical methods and assayed by cellular assays. Moreover, a highly sensitive ELISA for the detection of the P61S-tagged mutants in biological samples has been developed. Finally, we explored the pro-nociceptive effects elicited by hNGF mutants in vivo, demonstrating an expanded therapeutic window with a ten-fold increase in potency.This structure-activity relationship study has led to validate the concept of developing painless NGF as a therapeutic, targeting the NGF receptor system and supporting the choice of hNGF P61S R100E as the best candidate to advance in clinical development. Moreover, this study contributes to the identification of the molecular determinants modulating the properties of the hNGF "painless" mutants.

  3. HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of diabetic neuropathy.

    Science.gov (United States)

    Walwyn, W M; Matsuka, Y; Arai, D; Bloom, D C; Lam, H; Tran, C; Spigelman, I; Maidment, N T

    2006-03-01

    A previous phase III clinical trial failed to show significant therapeutic benefit of repeated subcutaneous nerve growth factor (NGF) administration in the treatment of diabetic neuropathy. Animal studies have since shown that site-specific viral-mediated expression of NGF in the lumbar dorsal root ganglia prevents peripheral nerve dysfunction associated with chemically induced neuropathy. Using a Herpes simplex virus expression vector, we have investigated the effect of localized NGF expression in a genetic mouse model of progressive diabetic neuropathy, the +/+ Leprdb mouse. We found that site-specific delivery of NGF initially delayed the appearance of hypoalgesia, assessed by the Hargreaves test, by 1 month and effectively attenuated this deficit for 2 months over the approximately 10 months normal life-span of these animals. Once the disease progressed into its more severe stages, NGF, although still capable of altering the electrophysiological profile of the sensory A- and C-fibers and influencing the expression of p75 and substance P in the dorsal root ganglia, could no longer maintain normal nociception. These data suggest that maximal therapeutic benefit in future NGF-based gene therapy trials will be gained from early applications of such viral-mediated neurotrophin delivery.

  4. Expression of nerve growth factor (NGF) isoforms in the rat uterus during pregnancy: accumulation of precursor proNGF.

    Science.gov (United States)

    Lobos, Edgar; Gebhardt, Claudia; Kluge, Annett; Spanel-Borowski, Katharina

    2005-04-01

    The mechanisms that promote the transient degenerative changes in the uterus innervation during pregnancy remain incompletely understood. Signaling by the nerve growth factor (NGF)-beta is important for maintaining the density of peripheral sympathetic innervation. Here, we analyzed the spatial and temporal expression of NGF isoforms in the rat uterus using RT-PCR, immunoblot analysis, and immunohistochemistry during pregnancy (d 7, 14, and 21), and postpartum (d 1, 8, and 22). Western blot analysis using antibodies to mature NGF-beta and to proNGF domain demonstrated a significant decrease in mature NGF-beta at gestational d 14 and 21 (term pregnancy) and 1 d postpartum, which paralleled a remarkable accumulation of the 26-28-, 32-, and 60-kDa proNGF forms. There were diminished ratios of mature NGF-beta to proNGF independent of uterus growth on the same gestational days. Immunohistochemistry revealed a progressive NGF-beta decline throughout pregnancy in the myometrium and a near absence at term pregnancy, which contrasted with increased NGF immunostaining in the intermyometrial connective tissue layers. More importantly, proNGF-specific antibodies identified the increased NGF immunoreactivity in the intermyometrial layers at term pregnancy as proNGF and not mature NGF-beta. Alterations in the processing of NGF and accumulation of proNGF in the intermyometrial layers, where axonal degeneration occurs, may contribute significantly to the pregnancy-related uterine denervation and to the control of myometrial activity.

  5. Intravitreal live adult Brugian filariasis

    Directory of Open Access Journals (Sweden)

    Rao Nageswar

    2008-01-01

    Full Text Available Human ocular infestation by live filarial worm is a rare occurrence and has been reported mostly form South-East Asia. It involves the eyelids, conjunctiva, cornea, anterior chamber and uvea. No case of intravitreal Brugian microfilaria / adult worm has been found by Medline search. Here we report a case of live intravitreal adult Brugian filaria, where the parasite was successfully removed by pars plana vitrectomy. Identification of the worm was done by light microscopy and confirmed by immuno chromatographic test.

  6. Characterization of antibodies to synthetic nerve growth factor (NGF) and proNGF peptides.

    Science.gov (United States)

    Ebendal, T; Persson, H; Larhammar, D; Lundströmer, K; Olson, L

    1989-03-01

    Sequence data for the mature nerve growth factor (NGF) protein and its precursor are available from molecular cloning of the NGF gene in several species, including mice, humans, rats, and chickens. Hydrophilicity analysis of the predicted rat and chicken prepro-NGF was carried out to locate putative antigenic determinants. Eight peptides were selected and synthesized based on hydrophilicity profiles. Two peptides represent sequences in the rat (and mouse) pro-NGF, one peptide (our peptide P3) represents a highly conserved region of the mature NGF protein (identical in humans, mice, rats, and chickens), two peptides are specific for the mature chicken NGF, and the remaining three peptides are specific for the mature rat NGF (each with only one amino acid substitution compared with corresponding segments of the mouse NGF). For immunization, the peptides were conjugated to keyhold limpet hemocyanin and used to produce antisera in rabbits. After bleeding, peptide-specific antibodies were purified on affinity columns prepared by coupling each of the synthetic peptides. The different peptide antisera and affinity-purified antibodies then were characterized by enzyme-linked immunoassay (ELISA) and immunohistochemistry of the male mouse submandibular gland, a rich exocrine source of NGF. ELISA analysis showed that all peptide antisera bound two to four orders of magnitude better than normal rabbit serum to a coat of their proper peptide. The higher binding was retained by the purified peptide antibodies compared with normal rabbit immunoglobulin. Specific tests, in which one peptide antiserum was checked against different peptide coats in the ELISA, also showed two to four orders of magnitude higher binding of antibodies to the proper synthetic peptide. The peptide antibodies also were tested for their ability to bind to native mouse beta NGF coated to the immunoplates. Only antibodies raised to the conserved P3 peptide recognized native NGF to an extent similar to that

  7. Interaction of antibodies to synthetic peptides of proNGF with in vitro synthesized NGF precursors.

    Science.gov (United States)

    Dicou, E

    1989-09-25

    Sera raised against three synthetic peptides that reproduce sequences of the pro-nerve growth factor (proNGF) protein were tested in immunoprecipitation experiments using in vitro translation products of SP6-directed NGF mRNA in a rabbit reticulocyte lysate. The interaction of these antibodies with bacterially synthesized chimeric preproNGF was also examined. Digestion of the translation products by the gamma-subunit generated the 22 and 18 kDa intermediates. A predominant 13 kDa intermediate was obtained after digestion of translation products in wheat germ extract. This is shown to be the N-terminal peptide by immunoprecipitation with an anti-peptide serum. These antibodies may be used to detect NGF precursor cleavage products in vivo.

  8. Dynamic structure of NGF and proNGF complexed with p75NTR

    DEFF Research Database (Denmark)

    Pimenta, A C; Dourado, D F A R; da Silva Martins, João Miguel;

    2014-01-01

    Crystallographic structures of NGF/p75NTR and proNGF/p75NTR were previously obtained in 2:1 and 2:2 stoichiometries, respectively. However, evidence shows that both stoichiometries can occur for mature neurotrophins and pro-neurotrophins. We used Molecular Dynamics (MD) simulations to examine......, where different stoichiometries induce conformational changes that might be the basis for the different biological outcomes observed with the mature and proforms of neurotrophins....

  9. Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.

    Science.gov (United States)

    Del Amo, Eva M; Urtti, Arto

    2015-08-01

    Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics.

  10. Experiment Study of Retinal Ultrastructure after Intravitreal FK506

    Institute of Scientific and Technical Information of China (English)

    Shuangnong Li; Shibo Tang; Wei Li; Dongping Li

    2004-01-01

    Purpose:To investigate the retinal toxicity of FK506 by intravitreal administration.Methods :Twenty-two eyes of 14 New Zealand rabbits were investigated. FK506 at con centrations of 5,25 and 50μg/eye was injected into the vitreous cavitiesrespectively.The control eyes were received mixed solution of balanced salt and ethanol. All eyes were examined by tonometry, slit lamp and indirect ophthalmoscopy preoperatively and post operatively at the 1st, 3rd, 7th, and 14th day respectively. In the final examination, all eyes were enucleated and processed for light and electron microscopy. Conclusion: It is safety with intravitreal FK506. There are no irritation and toxicity to the are proved to be toxic to the retina. Eye Science 2004;20:34-38.

  11. Intravitreal Bevacizumab (Avastin for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    Directory of Open Access Journals (Sweden)

    J. Fernando Arevalo

    2011-01-01

    Full Text Available This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB on diabetic retinopathy (DR including diabetic macular edema (DME and proliferative diabetic retinopathy (PDR at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD, and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy.

  12. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    Science.gov (United States)

    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  13. Gene Transfer and Molecular Cloning of the Human NGF Receptor

    Science.gov (United States)

    Chao, Moses V.; Bothwell, Mark A.; Ross, Alonzo H.; Koprowski, Hilary; Lanahan, Anthony A.; Buck, C. Randall; Sehgal, Amita

    1986-04-01

    Nerve growth factor (NGF) and its receptor are important in the development of cells derived from the neural crest. Mouse L cell transformants have been generated that stably express the human NGF receptor gene transfer with total human DNA. Affinity cross-linking, metabolic labeling and immunoprecipitation, and equilibrium binding with 125I-labeled NGF revealed that this NGF receptor had the same size and binding characteristics as the receptor from human melanoma cells and rat PC12 cells. The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe. A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor.

  14. Medial-to-lateral gradient of neostriatal NGF receptors: relationship to cholinergic neurons and NGF-like immunoreactivity.

    Science.gov (United States)

    Altar, C A; Dugich-Djordjevic, M; Armanini, M; Bakhit, C

    1991-03-01

    High-affinity binding sites for recombinant human NGF (rhNGF) were studied in the caudate-putamen of the adult rat and rabbit. Displaceable 125I-rhNGF binding sites were densely distributed throughout the caudate-putamen and were 2-3-fold more prevalant in the ventrolateral and lateral than in the medial caudate-putamen. The amount of nondisplaceable binding did not vary throughout the caudate-putamen. The medial-to-lateral receptor gradient was correlated (r = +0.99) with a 2-3-fold medial-to-lateral increase in ChAT activity. In contrast, NGF-like immunoreactivity (NGF-LI) was prevalent but uniformly distributed in the caudate-putamen. Lesions of intrinsic cholinergic neurons by quinolinic acid produced extensive gliosis in the medial, central, and lateral caudate-putamen, yet 125I-rhNGF binding was decreased in each of these regions. The activity of ChAT and 125I-rhNGF binding throughout the caudate-putamen were each decreased by 40% following quinolinic acid. Binding was not changed after 70-77% dopamine nerve terminal depletions induced by 6-hydroxydopamine, demonstrating a nonglial, nondopaminergic locus for striatal NGF binding sites. The cholinergiclike topography of NGF binding sites throughout the intact caudate-putamen, the parallel decreases of cholinergic neurons and NGF binding sites following intrinsic neuronal loss, and the uniform neostriatal gradient of NGF-LI are consistent with the trophic role of endogenous NGF for cholinergic interneurons of the caudate-putamen.

  15. Ginger improves cognitive function via NGF-induced ERK/CREB activation in the hippocampus of the mouse.

    Science.gov (United States)

    Lim, Soonmin; Moon, Minho; Oh, Hyein; Kim, Hyo Geun; Kim, Sun Yeou; Oh, Myung Sook

    2014-10-01

    Ginger (the rhizome of Zingiber officinale Roscoe) has been used worldwide for many centuries in cooking and for treatment of several diseases. The main pharmacological properties of ginger include anti-inflammatory, antihyperglycemic, antiarthritic, antiemetic and neuroprotective actions. Recent studies demonstrated that ginger significantly enhances cognitive function in various cognitive disorders as well as in healthy brain. However, the biochemical mechanisms underlying the ginger-mediated enhancement of cognition have not yet been studied in normal or diseased brain. In the present study, we assessed the memory-enhancing effects of dried ginger extract (GE) in a model of scopolamine-induced memory deficits and in normal animals by performing a novel object recognition test. We found that GE administration significantly improved the ability of mice to recognize novel objects, indicating improvements in learning and memory. Furthermore, to elucidate the mechanisms of GE-mediated cognitive enhancement, we focused on nerve growth factor (NGF)-induced signaling pathways. NGF enzyme-linked immunosorbent assay analysis revealed that GE administration led to elevated NGF levels in both the mouse hippocampus and rat glioma C6 cells. GE administration also resulted in phosphorylation of extracellular-signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB), as revealed by Western blotting analysis. Neutralization of NGF with a specific NGF antibody inhibited GE-triggered activation of ERK and CREB in the hippocampus. Also, GE treatment significantly increased pre- and postsynaptic markers, synaptophysin and PSD-95, which are related to synapse formation in the brain. These data suggest that GE has a synaptogenic effect via NGF-induced ERK/CREB activation, resulting in memory enhancement.

  16. Triptolide upregulates NGF synthesis in rat astrocyte cultures.

    Science.gov (United States)

    Xue, Bing; Jiao, Jian; Zhang, Lei; Li, Kai-Rong; Gong, Yun-Tao; Xie, Jun-Xia; Wang, Xiao-Min

    2007-07-01

    Triptolide (T10), an extract from the traditional Chinese herb, Tripterygium wilfordii Hook F (TWHF), has been shown to attenuate the rotational behavior induced by D: -amphetamine and prevent the loss of dopaminergic neurons in the substantia nigra in rat models of Parkinson's disease. To examine if the neuroprotective effect is mediated by its stimulation of production of neurotrophic factors from astrocytes, we investigated the effect of T10 on synthesis and release of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in rat astrocyte cultures. T10 did not affect the synthesis and release of either BDNF or GDNF. However, it significantly increased NGF mRNA expression. It also increased both intracellular NGF and NGF level in culture medium. These results indicate that the neuroprotective effect of T10 might be mediated, at least in part, via a stimulation of the production and release of NGF in astrocytes.

  17. Expression of NGF, Trka and p75 in human cartilage

    Directory of Open Access Journals (Sweden)

    A Gigante

    2009-06-01

    Full Text Available Nerve growth factor (NGF exerts its action through two types of receptor: high-affinity tyrosine kinase A receptor (trkA and low-affinity p75 receptor. NGF has a neurotrophic role in central and peripheral nervous system development, but there is also clear evidence of its involvement in the developing skeleton. The aim of the present immunohistochemical study was to investigate the expression and distribution of NGF, trkA, and p75 in normal cartilaginous tissues from adult subjects: articular and meniscal cartilage of the knee, cartilage from the epiglottis, and intervertebral disc tissue. Detection of NGF mRNA was also performed by in situ hybridization. Immunoreaction for NGF and the two receptors in articular chondrocytes, chondrocyte-like cells of meniscus and annulus fibrosus, and chondrocytes of the epiglottis demonstrated that they are all expressed in hyaline, fibrous and elastic cartilaginous tissues, suggesting that they could be involved in cartilage physio-pathology.

  18. Functional Characterization of Human ProNGF and NGF Mutants: Identification of NGF P61SR100E as a “Painless” Lead Investigational Candidate for Therapeutic Applications

    Science.gov (United States)

    Bruni Ercole, Bruno; Materazzi, Serena; Nassini, Romina; Coppi, Elisabetta; Patacchini, Riccardo; Capsoni, Simona; Lamba, Doriano; Cattaneo, Antonino

    2015-01-01

    Background Nerve Growth Factor (NGF) holds a great therapeutic promise for Alzheimer's disease, diabetic neuropathies, ophthalmic diseases, dermatological ulcers. However, the necessity for systemic delivery has hampered the clinical applications of NGF due to its potent pro-nociceptive action. A “painless” human NGF (hNGF R100E) mutant has been engineered. It has equal neurotrophic potency to hNGF but a lower nociceptive activity. We previously described and characterized the neurotrophic and nociceptive properties also of the hNGF P61S and P61SR100E mutants, selectively detectable against wild type hNGF. However, the reduced pain-sensitizing potency of the “painless” hNGF mutants has not been quantified. Objectives and Results Aiming at the therapeutic application of the “painless” hNGF mutants, we report on the comparative functional characterization of the precursor and mature forms of the mutants hNGF R100E and hNGF P61SR100E as therapeutic candidates, also in comparison to wild type hNGF and to hNGF P61S. The mutants were assessed by a number of biochemical, biophysical methods and assayed by cellular assays. Moreover, a highly sensitive ELISA for the detection of the P61S-tagged mutants in biological samples has been developed. Finally, we explored the pro-nociceptive effects elicited by hNGF mutants in vivo, demonstrating an expanded therapeutic window with a ten-fold increase in potency. Conclusions This structure-activity relationship study has led to validate the concept of developing painless NGF as a therapeutic, targeting the NGF receptor system and supporting the choice of hNGF P61S R100E as the best candidate to advance in clinical development. Moreover, this study contributes to the identification of the molecular determinants modulating the properties of the hNGF “painless” mutants. PMID:26371475

  19. Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis

    NARCIS (Netherlands)

    I.M. Gan; J.T. van Dissel (Jaap); W.H. Beekhuis (Houdijn); W. Swart; J.C. van Meurs (Jan)

    2001-01-01

    textabstractBACKGROUND/AIMS: To study the intravitreal antibiotic concentrations and the efficacy of an intravitreal dosing regimen to treat patients with postoperative bacterial endophthalmitis. This regimen, based on pharmacokinetic/pharmacodynamic considerations, relies on a

  20. Intravitreal Daptomycin for Recalcitrant Postoperative Endophthalmitis

    Directory of Open Access Journals (Sweden)

    Jennifer M. Sim

    2016-02-01

    Full Text Available Purpose: To report the first case to our knowledge of intravitreal daptomycin used to successfully treat culture-negative vancomycin resistant to exogenous endophthalmitis. Methods: Case report with preoperative, intraoperative, and postoperative findings. Results: A 63-year-old Caucasian male underwent routine pars plana vitrectomy with epiretinal membrane peeling. He developed acute postoperative endophthalmitis, and underwent vitreous tap and injection of intravitreal vancomycin/ceftazidime/dexamethasone. Gram stain showed Gram-positive cocci, but cultures were negative. His infection subsequently proved very recalcitrant and his treatment course involved pars plana vitrectomy with anterior chamber washout and repeat injection of antibiotics, followed by repeat intravitreal vancomycin and ceftazidime. Ultimately, a second vitrectomy with intravitreal daptomycin controlled his intraocular infection. On each occasion, cultures were negative. Conclusion: This case suggests that vancomycin resistance should be considered in culture-negative postoperative endophthalmitis, and intravitreal daptomycin should be considered as an important treatment alternative. Although vancomycin resistance is fairly rare in endophthalmitis, acknowledgment of its increasing occurrence rate is critical for optimal management.

  1. Choroidal Thickness Changes After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration.

    Science.gov (United States)

    Minnella, Angelo Maria; Federici, Matteo; Falsini, Benedetto; Barbano, Lucilla; Gambini, Gloria; Lanza, Angela; Caporossi, Aldo; Savastano, Maria Cristina

    2016-08-01

    The results regarding changes of choroidal thickness following intravitreal ranibizumab injections in the literature are controversial. Vascular endothelial growth factor A is implicated in pathogenesis of neovascular age-related macular degeneration (AMD). The suspected unchanged choroidal layer thickness after intravitreal injections of ranibizumab suggests a possible protection of the outer blood-retinal barrier in the human eye. The aim was to evaluate choroidal thickness following the first administration of the study drug ranibizumab into the eyes of naïve wet AMD patients (nAMD). In this open label, 3-month, prospective, single-center, interventional, single-arm pilot study, 20 nAMD eyes were included and underwent three consecutive monthly injections of ranibizumab (0.5 mg/0.05 ml). Vital signs (i.e., blood pressure and pulse), ophthalmic examinations, intraocular pressure, best correct visual acuity and subfoveal choroidal thickness as examined with optical coherence tomography using enhanced depth imaging (OCT-EDI) were assessed at each visit. All patients were evaluated at baseline and at 15, 30 60 and 90 days after intravitreal injection. Ten eyes with fibrotic AMD lesions were evaluated as the control group. In all eyes, the choroidal thicknesses (µm) exhibited no significant changes from the baseline visit to the visits at 15, 30, 60 and 90 days post-injection (P > 0.05). The intravitreal treatment with ranibizumab was well tolerated, and no adverse events were registered. Choroidal thickness appeared to be unmodified following the intravitreal injection of ranibizumab into nAMD eyes. Intravitreal ranibizumab injections probably elicit a pharmacologic effect only in the choroidal neovascularization and not in the choroid circulation under neovascular lesions. Clinical Trials Eudract Registration #: 2013-005091-17.

  2. [The results of intravitreal bevacizumab in subretinal neovascularisation in angioid streaks].

    Science.gov (United States)

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    To assess the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization (CNV) due to angioid streaks; To assess the safety and results stability; Prospective, nonrandomized, interventional case study on choroidal neovascularization due to angioid streaks treated with intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. 8 cases with CNV associated to angioid streaks were evaluated between January 2007 and January 2013. Mean age of patients in the study was 52,36 +/- 4,33 years (ranging 42-64 years). The mean number of intravitreal injections was 4.64 +/- 0,42 (ranging between 3-8 injections). Mean visual acuity improved significantly in all cases after 3 intravitreal injections with a gain of more than 15 letters in 6 out of 8 cases (75%). OCT confirmed reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the CNV reoccurred in 5 out of 8 cases (62.5%) requiring additional treatment. 3 out of 8 cases finally lost more than 5 letters due to subretinal fibrosis. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the CNV due to angioid streaks. High recurrence rate and quick lesion progression to subretinal fibrosis might be responsible for long-term poor functional results in this type of CNVs. More cases are needed for validation.

  3. Rabbit facial nerve regeneration in NGF-containing silastic tubes.

    Science.gov (United States)

    Spector, J G; Lee, P; Derby, A; Frierdich, G E; Neises, G; Roufa, D G

    1993-05-01

    Previous reports suggest that exogenous nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. Rabbit facial nerve regeneration in 10-mm Silastic tubes prefilled with NGF was compared to cytochrome C (Cyt. C), bridging an 8-mm nerve gap. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than cytochrome-C-treated controls. Morphometric analysis at the midtube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and cytochrome-C-treated implants. However, when the number of myelinated fibers in 5-week regenerates were compared to their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than cytochrome-C--treated implants (46% vs. 18%, respectively). In addition, NGF-containing chambers reinnervated a higher percentage of myelinated axons in the distal transected neural stumps (49% vs. 34%). Behavioral and electrophysiologic studies demonstrated spontaneous and induced activities in the target muscles when approximately one third of the myelinated axons were recovered in the midchamber (1280 axons). Horseradish peroxidase (HRP) studies demonstrated retrograde axonal transport to the midchamber and proximal transected neural stump. PC12 bioassay demonstrated persistent NGF activity in the intrachamber fluids at 3 (5:1 dilution) and 5 (2:1 dilution) weeks of entubation. Electrophysiologic tests demonstrated a slow conduction velocity of a propagated electrical impulse (43.5 m/s-1 vs. 67 m/s-1) and shallow wide compound action potential. In wider defects (15-mm chambers) and longer entubation periods (7 weeks), no regeneration or NGF activity was seen. Therefore, exogenous NGF provides an early but limited neurotrophic effect on the regeneration of the rabbit buccal division of the facial nerve and a

  4. HCMV Infection Depress NGF Expression in Human Glioma Cells

    Institute of Scientific and Technical Information of China (English)

    Hai-tao WANG; Bin WANG; Zhi-jun LIU; Zhi-qiang BAI; Ling LI; Dong-meng QIAN; Zhi-yong YAN; Xu-xia SONG

    2009-01-01

    Human cytomegalovirus (HCMV) is the most common cause of congenital infection, resulting in birth defects such as microcephaly. In this study, RT-PCR and Western Blotting were performed to quantify the regulation of endogenic nerve growth factor expression in neuroglia cells by HCMV infection. The results showed that basal, endogenous NGF expression in U251 was unchanged during early HCMV infection. NGF expression is strongly down-regulated during the latent phase of infection. These results suggest that HCMV can depress the NGF expression in U251 cells.

  5. NGF and BDNF long-term variations in the thyroid, testis and adrenal glands of a mouse model of fetal alcohol spectrum disorders

    Directory of Open Access Journals (Sweden)

    Mauro Ceccanti

    2013-12-01

    Full Text Available OBJECTIVES: Fetal Alcohol Spectrum Disorders (FASD due to prenatal ethanol consumption may induce long-lasting changes to the newborns affecting also the endocrine system and the nerve growth factor (NGF and brain derived neurotrophic factor (BDNF signaling. Thus the aim of this study was to investigate in the thyroid, testis and adrenal glands of a FASD mouse model the long-lasting effects of ethanol exposure during pregnancy and lactation on NGF and BDNF and their main receptors, TrkA and TrkB, including their phosphorylated patterns. METHODS: We used aged male CD-1 mice early exposed to ethanol solution or red wine at same ethanol concentration (11% vol. RESULTS We found elevations in NGF and BDNF in the thyroid of aged mice exposed to ethanol solution only but not in the red wine group. In the testis NGF resulted to be increased only in the ethanol solution group. In the adrenal glands data showed an elevation in NGF in both the ethanol solution group and red wine. No changes in TrkA, TrkB, phospho-TrkA and phospho-TrkB were revealed in all tissues examined. CONCLUSIONS Early administration of ethanol may induce long-lasting changes in the mouse thyroid, testis and adrenal glands at NGF and BDNF levels.

  6. Intravitreal Dexamethasone Implant (Ozurdex in Coats' Disease

    Directory of Open Access Journals (Sweden)

    Ali Osman Saatci

    2013-09-01

    Full Text Available We injected an intravitreal dexamethasone implant in two eyes of 2 pediatric patients with Coats' disease in addition to other treatment modalities, such as intravitreal ranibizumab injection and indirect laser photocoagulation. In both eyes, intraocular pressure moderately rose in a temporary fashion. The dexamethasone implant seems to be a valuable addition to the armamentarium of treatment options for Coats' disease as it necessitates fewer injections than anti-VEGF injections and thereby fewer sessions of general anesthesia in the pediatric population.

  7. Adverse skin reactions following intravitreal bevacizumab injection

    Science.gov (United States)

    Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A

    2011-01-01

    The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260

  8. Pharmacokinetics and safety of intravitreal caspofungin.

    Science.gov (United States)

    Shen, Ying-Cheng; Liang, Chiao-Ying; Wang, Chun-Yuan; Lin, Keng-Hung; Hsu, Min-Yen; Yuen, Hon-Leung; Wei, Li-Chen

    2014-12-01

    Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 μg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 μg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 μg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

  9. An Optimized Procedure for the Site-Directed Labeling of NGF and proNGF for Imaging Purposes

    Science.gov (United States)

    Di Matteo, Pierluigi; Calvello, Mariantonietta; Luin, Stefano; Marchetti, Laura; Cattaneo, Antonino

    2017-01-01

    Neurotrophins are growth factors of fundamental importance for the development, survival and maintenance of different neuronal and non-neuronal populations. Over the years, the use of labeled neurotrophins has helped in the study of their biological functions, leading to a better understanding of the processes that regulate their transport, traffic, and signaling. However, the diverse and heterogeneous neurotrophin labeling strategies adopted so far have often led to poorly reproducible protocols and sometimes conflicting conclusions. Here we present a robust, reliable, and fast method to obtain homogeneous preparations of fluorescent proNGF and NGF with 1:1 labeling stoichiometry. This strategy is well suited for several applications, ranging from advanced imaging techniques such as single particle tracking, to analyses that require large amounts of neurotrophins such as in vivo monitoring of protein biodistribution. As a proof of the quality of the labeled NGF and proNGF preparations, we provide a quantitative analysis of their colocalization with proteins involved in the signaling endosome function and sorting. This new analysis allowed demonstrating that proNGF localizes at a sub-population of endosomes not completely overlapped to the one hosting NGF. PMID:28210618

  10. Comparison of suprachoroidal drug delivery with subconjunctival and intravitreal routes using noninvasive fluorophotometry.

    Directory of Open Access Journals (Sweden)

    Puneet Tyagi

    Full Text Available PURPOSE: To determine whether exposure of sodium fluorescein (NaF to the choroid-retina region in the posterior segment of the eye is greater with suprachoroidal injection when compared to intravitreal and transscleral routes. METHODS: Suprachoroidal injection, a new approach for drug delivery to the posterior segment of the eye was validated using a 34 G needle and Indian ink injections in Sprague Dawley rats, followed by histology. Delivery of NaF was compared in Sprague Dawley rats after suprachoroidal, posterior subconjunctival, or intravitreal injections. NaF levels were monitored noninvasively up to 6 hours using Fluorotron Master™, an ocular fluorophotometer Pharmacokinetic parameters were estimated using WinNonlin. RESULTS: Histological analysis indicated localization of India ink to the suprachoroidal space below sclera, following injection. NaF delivery to choroid-retina was in the order: suprachoroidal > intravitreal >posterior subconjunctival injection. Peak NaF concentration (C(max in choroid-retina was 36-fold (p = 0.001 and 25-fold (p = 0.001 higher after suprachoroidal (2744±1111 ng/ml injection when compared to posterior subconjunctival (76±6 ng/ml and intravitreal (108±39 ng/ml injections, respectively. NaF exposure (AUC(0-360min to choroid-retina after suprachoroidal injection was 6-fold (p = 0.001 and 2-fold (p = 0.03 higher than posterior subconjunctival and intravitreal injections, respectively. Choroid-retina T(max was observed immediately after dosing with suprachoroidal injections and at 10 and 27.5 minutes, respectively, with subconjunctival and intravitreal injections. CONCLUSIONS: Suprachoroidal injections are feasible in a rat model. Suprachoroidal injections resulted in the highest bioavailability, that is, the extent and rate of delivery of NaF to choroid-retina, when compared to intravitreal and posterior subconjunctival injections. Ocular fluorophotometry is useful for noninvasive monitoring

  11. Intravitreal bevacizumab (avastin for circumscribed choroidal hemangioma

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    Subrata Mandal

    2011-01-01

    Full Text Available Circumscribed choroidal hemangiomas are rare ophthalmic entities that cause diminution in vision due to accumulation of subretinal and/or intraretinal fluid in the macular area. Various treatment options ranging from conventional laser to photodynamic therapy have been employed to destroy the tumor and reduce the exudation; however, either the inability to penetrate through the exudative fluid or the collateral retinal damage induced by these treatment modalities make them unsuitable for lesions within the macula. We evaluated the role of intravitreal bevacizumab, a pan-vascular endothelial growth factor (VEGF inhibitor, in reducing the sub- and intraretinal fluid in three patients with circumscribed choroidal hemangiomas. All the patients had complete resolution of the serous retinal detachment that was maintained till at least 12 months after the first injection. Intravitreal bevacizumab may be used in combination with thermal laser or photodynamic therapy in treating circumscribed choroidal hemangiomas with subretinal fluid.

  12. Response of diabetic papillopathy to intravitreal bevacizumab

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    Hassan Al-Dhibi

    2011-01-01

    Full Text Available Diabetic papillopathy is an uncommon hyperemic optic disc swelling that occurs in patients with long-standing diabetes, is typically self-resolving with minimal effect on vision, and is likely ischemic in origin. The purpose of the current report is to document the response of diabetic papillopathy to intravitreal injection of bevacizumab (Avastin, Genentech Inc, San Francisco, California, USA, a humanized monoclonal antibody to vascular endothelial growth factor.

  13. Response of Diabetic Papillopathy to Intravitreal Bevacizumab

    OpenAIRE

    Hassan Al-Dhibi; Khan, Arif O.

    2011-01-01

    Diabetic papillopathy is an uncommon hyperemic optic disc swelling that occurs in patients with long-standing diabetes, is typically self-resolving with minimal effect on vision, and is likely ischemic in origin. The purpose of the current report is to document the response of diabetic papillopathy to intravitreal injection of bevacizumab (Avastin, Genentech Inc, San Francisco, California, USA), a humanized monoclonal antibody to vascular endothelial growth factor.

  14. Intravitreal memantine retinal toxicity in rabbits.

    Science.gov (United States)

    Moreno Páramo, D; Reyna Vielma, S; Rodríguez Reyes, A; Hernández Ayuso, I; Quiroz Mercado, H

    2016-02-01

    To histologically evaluate whether the intravitreal application of memantine produces retinal toxicity in rabbits. A cross-sectional design, experimental, descriptive study was performed on 16 eyes of 16 New Zealand rabbits of 3 kg, divided in 4 groups of 4 rabbits. A dose of 70 ng/ml of intravitreal memantine was administered in Group A, a dose of 150 ng/ml in Group B, a dose of 400 ng/ml in Group C, and Group D received 1 ml of balanced salt solution. The injected eye of half of each group was enucleated 15 days after the injection, and the rest within 30 days after injection. Following enucleation, each eye was placed in 10% formaldehyde. Histopathological analysis was performed on all enucleated eyes. The animals were treated according to the guidelines of the Association for Research on Vision and Ophthalmology (ARVO). Groups A, B and D did not show any histopathological changes after their enucleation at 15 and 30 days. Group C showed changes in the photoreceptor layer after enucleation at 15 and 30 days. In our study, it was observed that memantine concentrations at 70 ng/ml and 150 ng/ml are safe when administered intravitreally; however, doses of 400 ng/ml produced retinal structural changes. This research should continue to assess its clinical usefulness. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  16. Improvement of sciatic nerve regeneration using laminin-binding human NGF-beta.

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    Wenjie Sun

    Full Text Available BACKGROUND: Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA, NGF-beta could target to nerve cells and improve nerve regeneration. METHODS: Laminin-binding assay and sustained release assay of NGF-beta fused with NtA (LBD-NGF from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested. FINDINGS: LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages. CONCLUSION: Fused with NtA, NGF-beta could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries.

  17. The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer's Disease.

    Science.gov (United States)

    Iulita, M Florencia; Cuello, A Claudio

    2016-01-01

    It is well established that individuals with Down syndrome develop Alzheimer's disease neuropathology by middle age. Both in Alzheimer's disease and Down syndrome, this is accompanied by the atrophy of NGF-dependent cholinergic neurons of the basal forebrain. An NGF trophic compromise in Alzheimer's disease had been early suspected. This hypothesis was discarded with the finding of unaltered NGF mRNA synthesis and of increased NGF precursor levels (proNGF) in postmortem Alzheimer's disease brains. The possibility of an NGF trophic disconnection has been recently revisited at the light of a newly discovered extracellular NGF metabolic pathway; where proNGF is released in an activity-dependent manner and converted by plasmin to mature NGF in the extracellular space. Mature NGF is ultimately degraded by the metalloprotease MMP-9. This pathway has been shown to be compromised in Alzheimer's disease and Down syndrome brains, thus reviving the trophic factor hypothesis to explain the atrophy of basal forebrain cholinergic neurons in these disorders. This chapter will discuss the physiological role of NGF and its biological significance to cholinergic neurons of the CNS, and present the evidence for a dysregulation of the NGF metabolism in Alzheimer's disease and Down syndrome.

  18. Protective effects of matrine on experimental autoimmune encephalomyelitis via regulation of ProNGF and NGF signaling.

    Science.gov (United States)

    Zhu, Lin; Pan, Qing-xia; Zhang, Xiao-Jian; Xu, Yu-Ming; Chu, Yao-juan; Liu, Nan; Lv, Peng; Zhang, Guang-Xian; Kan, Quan-Cheng

    2016-04-01

    Inflammation, demyelination, oligodendrocyte (OLG) death, and axonal degeneration are primary characteristics of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). OLGs generate myelin sheaths that surround axons, while damage to OLGs leads to demyelination and neurological functional deficit. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to effectively ameliorate clinical signs in EAE. Its therapeutic mechanism has, however, not been completely elucidated. In the present study, we found that MAT retarded the disease process, attenuated the clinical severity of EAE rats, ameliorated inflammation and demyelination, and suppressed the apoptosis of OLGs in the central nervous system (CNS) of EAE rats. In addition, MAT markedly blocked increased expression of the proNGF-p75(NTR) death signaling complex, which is known to mediate OLG death in EAE animals. At the same time, MAT also prevented a decrease in the levels of NGF and its receptor TrkA, which together mediate the cell survival pathway and differentiation of OLGs. ProNGF, NGF, and the downstream effector proteins play an important role in the growth, differentiation, and apoptosis of OLGs as well as the reparative response to neuronal damage. These findings thus indicate that MAT improves clinical severity of EAE in part by reducing OLG apoptosis via restoring the ratios of proNGF:NGF and the respective receptors p75(NTR):TrkA in vivo. Taken together, these results suggest that MAT may be a promising agent for MS treatment based on its protective effect on OLGs.

  19. Micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system.

    Science.gov (United States)

    Ma, Feiyan; Nan, Kaihui; Lee, SuNa; Beadle, James R; Hou, Huiyuan; Freeman, William R; Hostetler, Karl Y; Cheng, Lingyun

    2015-01-01

    There still is an unmet need for a safe and sustained intravitreal drug delivery system. In this study we are proposing and characterizing a micelle based, clear-media intravitreal drug delivery system using the lipid derivatized nucleoside analog, hexadecyloxypropyl-cidofovir (HDP-CDV, CMX 001). HDP-CDV forms micelles in water and in vitreous supernatant with the critical micelle concentration of 19 μg/mL and 9 μg/mL, respectively at 37 °C. The formed micelles had the average size of 274.7 nm and the Zeta potential of -47.1 mV. Drug release study in the excised rabbit vitreous showed a sustained release profile with a half-life of 2.7 days. The micelle formulation of HDP-CDV demonstrated a good safety profile in two animal species (rabbit and guinea pig) following intravitreal injection. The sustained efficacy was tested in a pretreatment study design and the drug potency was tested in an ongoing herpes simplex virus (HSV-1) retinitis model. The pretreatment studies using single intravitreal injection and later HSV-1 infection revealed at least 9 weeks of vitreous presence and therapeutic level of HDP-CDV, with 71% eyes protection from infection. The treatment study demonstrated that intravitreal administration halted active HSV-1 retinitis in 80% of the infected eyes while cidofovir (CDV) treatment failed to suppress active HSV-1 retinitis. In summary, lipid derivatized nucleoside analogs can be formulated as a micelle intravitreal injection and provides a sustained drug release in vitreous for chronic retinal diseases.

  20. Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

    Directory of Open Access Journals (Sweden)

    Zhuo Ye

    2015-08-01

    Full Text Available AIM:To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid (PLGA microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.METHODS:Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.RESULTS:The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05. The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form.CONCLUSION: The result of

  1. Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

    Institute of Scientific and Technical Information of China (English)

    Zhuo; Ye; Yan-Li; Ji; Xiang; Ma; Jian-Guo; Wen; Wei; Wei; Shu-Man; Huang

    2015-01-01

    · AIM: To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly(L-lactic-co-glycolic acid)(PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.·METHODS: Bevacizumab was encapsulated into PLGA microsphere via the solid- in- oil- in- hydrophilic oil(S/O/h O) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at day 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.·RESULTS: The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than thatof bevacizumab solution. The T1/2of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2of intravitreal injection of soluble bevacizumab is 3.91 d in vitreous and4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes(P <0.05). The AUC0-tof the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly.The immunofluorescence staining of PLGA-encapsulated bevacizumab(b-PLGA) in rabbit eye tissues was still observed up to 42 d. It was longer than that of the soluble form.· CONCLUSION: The result of this

  2. Taking pain out of NGF: a "painless" NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity.

    Directory of Open Access Journals (Sweden)

    Simona Capsoni

    Full Text Available During adulthood, the neurotrophin Nerve Growth Factor (NGF sensitizes nociceptors, thereby increasing the response to noxious stimuli. The relationship between NGF and pain is supported by genetic evidence: mutations in the NGF TrkA receptor in patients affected by an hereditary rare disease (Hereditary Sensory and Autonomic Neuropathy type IV, HSAN IV determine a congenital form of severe pain insensitivity, with mental retardation, while a mutation in NGFB gene, leading to the aminoacid substitution R100W in mature NGF, determines a similar loss of pain perception, without overt cognitive neurological defects (HSAN V. The R100W mutation provokes a reduced processing of proNGF to mature NGF in cultured cells and a higher percentage of neurotrophin secreted is in the proNGF form. Moreover, using Surface Plasmon Resonance we showed that the R100W mutation does not affect NGF binding to TrkA, while it abolishes NGF binding to p75NTR receptors. However, it remains to be clarified whether the major impact of the mutation is on the biological function of proNGF or of mature NGF and to what extent the effects of the R100W mutation on the HSAN V clinical phenotype are developmental, or whether they reflect an impaired effectiveness of NGF to regulate and mediate nociceptive transmission in adult sensory neurons. Here we show that the R100 mutation selectively alters some of the signaling pathways activated downstream of TrkA NGF receptors. NGFR100 mutants maintain identical neurotrophic and neuroprotective properties in a variety of cell assays, while displaying a significantly reduced pain-inducing activity in vivo (n = 8-10 mice/group. We also show that proNGF has a significantly reduced nociceptive activity, with respect to NGF. Both sets of results jointly contribute to elucidating the mechanisms underlying the clinical HSAN V manifestations, and to clarifying which receptors and intracellular signaling cascades participate in the pain

  3. The Role of Nerve Growth Factor (NGF and Its Precursor Forms in Oral Wound Healing

    Directory of Open Access Journals (Sweden)

    Karl Schenck

    2017-02-01

    Full Text Available Nerve growth factor (NGF and its different precursor forms are secreted into human saliva by salivary glands and are also produced by an array of cells in the tissues of the oral cavity. The major forms of NGF in human saliva are forms of pro-nerve growth factor (pro-NGF and not mature NGF. The NGF receptors tropomyosin-related kinase A (TrkA and p75 neurotrophin receptor (p75NTR are widely expressed on cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts and leukocytes, and in ductal and acinar cells of all types of salivary glands. In vitro models show that NGF can contribute at most stages in the oral wound healing process: restitution, cell survival, apoptosis, cellular proliferation, inflammation, angiogenesis and tissue remodeling. NGF may therefore take part in the effective wound healing in the oral cavity that occurs with little scarring. As pro-NGF forms appear to be the major form of NGF in human saliva, efforts should be made to study its function, specifically in the process of wound healing. In addition, animal and clinical studies should be initiated to examine if topical application of pro-NGF or NGF can be a therapy for chronic oral ulcerations and wounds.

  4. The Role of Nerve Growth Factor (NGF) and Its Precursor Forms in Oral Wound Healing.

    Science.gov (United States)

    Schenck, Karl; Schreurs, Olav; Hayashi, Katsuhiko; Helgeland, Kristen

    2017-02-11

    Nerve growth factor (NGF) and its different precursor forms are secreted into human saliva by salivary glands and are also produced by an array of cells in the tissues of the oral cavity. The major forms of NGF in human saliva are forms of pro-nerve growth factor (pro-NGF) and not mature NGF. The NGF receptors tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptor (p75(NTR)) are widely expressed on cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts and leukocytes, and in ductal and acinar cells of all types of salivary glands. In vitro models show that NGF can contribute at most stages in the oral wound healing process: restitution, cell survival, apoptosis, cellular proliferation, inflammation, angiogenesis and tissue remodeling. NGF may therefore take part in the effective wound healing in the oral cavity that occurs with little scarring. As pro-NGF forms appear to be the major form of NGF in human saliva, efforts should be made to study its function, specifically in the process of wound healing. In addition, animal and clinical studies should be initiated to examine if topical application of pro-NGF or NGF can be a therapy for chronic oral ulcerations and wounds.

  5. Gangliosides, NGF, brain aging and disease: a mini-review with personal reflections.

    Science.gov (United States)

    Cuello, A Claudio

    2012-06-01

    In this mini-review I summarize our research efforts in ascertaining the possible neuro-reparative properties of the GM1 ganglioside and its cooperative effects with NGF in stroke-lesion models. We also review aspects of our NGF investigations which have recently led to the discovery that NGF is released in an activity-dependent manner in the form of its precursor molecule, proNGF. These studies support the notion that in the CNS NGF metabolism conversion and degradation occur in the extracellular milieu. We have also validated this pathway in vivo demonstrating that the pharmacological inhibition of the pro-to mature NGF conversion results in the brain accumulation of proNGF and loss and atrophy of cortical cholinergic synapses. Furthermore, we have gathered neurochemical evidence for a compromise of this newly discovered NGF metabolic pathway in Alzheimer's disease, explaining the vulnerability of NGF-dependent forebrain cholinergic neurons in this disease despite normal NGF synthesis and abundance of NGF precursor.

  6. Cholinergic involvement in Alzheimer's disease. A link with NGF maturation and degradation.

    Science.gov (United States)

    Cuello, A Claudio; Bruno, Martin A; Allard, Simon; Leon, Wanda; Iulita, M Florencia

    2010-01-01

    Basal forebrain cholinergic neurons are highly dependent on nerve growth factor (NGF) supply for the maintenance of their cholinergic phenotype as well as their cholinergic synaptic integrity. The precursor form of NGF, proNGF, abounds in the CNS and is highly elevated in Alzheimer's disease. In order to obtain a deeper understanding of the NGF biology in the CNS, we have performed a series of ex vivo and in vivo investigations to elucidate the mechanisms of release, maturation and degradation of this neurotrophin. In this short review, we describe this NGF metabolic pathway, its significance for the maintenance of basal cholinergic neurons, and its dysregulation in Alzheimer's disease. We are proposing that the conversion of proNGF to mature NGF occurs in the extracellular space by the coordinated action of zymogens, convertases, and endogenous regulators, which are released in the extracellular space in an activity-dependent fashion. We further discuss our findings of a diminished conversion of the NGF precursor molecule to its mature form in Alzheimer's disease as well as an augmented degradation of mature NGF. These combined effects on NGF metabolism would explain the well-known cholinergic atrophy found in Alzheimer's disease and would offer new therapeutic opportunities aimed at correcting the NGF dysmetabolism along with Abeta-induced inflammatory responses.

  7. The Role of Nerve Growth Factor (NGF) and Its Precursor Forms in Oral Wound Healing

    Science.gov (United States)

    Schenck, Karl; Schreurs, Olav; Hayashi, Katsuhiko; Helgeland, Kristen

    2017-01-01

    Nerve growth factor (NGF) and its different precursor forms are secreted into human saliva by salivary glands and are also produced by an array of cells in the tissues of the oral cavity. The major forms of NGF in human saliva are forms of pro-nerve growth factor (pro-NGF) and not mature NGF. The NGF receptors tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptor (p75NTR) are widely expressed on cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts and leukocytes, and in ductal and acinar cells of all types of salivary glands. In vitro models show that NGF can contribute at most stages in the oral wound healing process: restitution, cell survival, apoptosis, cellular proliferation, inflammation, angiogenesis and tissue remodeling. NGF may therefore take part in the effective wound healing in the oral cavity that occurs with little scarring. As pro-NGF forms appear to be the major form of NGF in human saliva, efforts should be made to study its function, specifically in the process of wound healing. In addition, animal and clinical studies should be initiated to examine if topical application of pro-NGF or NGF can be a therapy for chronic oral ulcerations and wounds. PMID:28208669

  8. Chronic nicotine improves working and reference memory performance and reduces hippocampal NGF in aged female rats.

    Science.gov (United States)

    French, Kristen L; Granholm, Ann-Charlotte E; Moore, Alfred B; Nelson, Matthew E; Bimonte-Nelson, Heather A

    2006-05-15

    The cholinergic system is involved in cognition and several forms of dementia, including Alzheimer's disease, and nicotine administration has been shown to improve cognitive performance in both humans and rodents. While experiments with humans have shown that nicotine improves the ability to handle an increasing working memory load, little work has been done in animal models evaluating nicotine effects on performance as working memory load increases. In this report, we demonstrate that in aged rats nicotine improved the ability to handle an increasing working memory load as well as enhanced performance on the reference memory component of the water radial arm maze task. The dose required to exert these effects (0.3mg/kg/day) was much lower than doses shown to be effective in young rats and appears to be a lower maintenance dose than is seen in light to moderate smokers. In addition, our study reports a nicotine-induced reduction in nerve growth factor (NGF) protein levels in the hippocampus of the aged rat. The effects of nicotine on hippocampal NGF levels are discussed as a potential mechanism of nicotine-induced improvements in working and reference memory.

  9. The role of intravitreal chemotherapy for retinoblastoma

    Directory of Open Access Journals (Sweden)

    Fairooz P Manjandavida

    2015-01-01

    Full Text Available Targeted therapy in retinoblastoma (RB is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC, retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

  10. Intravitreal triamcinolone for diffuse diabetic macular oedema.

    LENUS (Irish Health Repository)

    Gibran, S K

    2012-02-03

    AIM: To evaluate the efficacy of intravitreal triamcinolone (IVTA) for the treatment of diffuse diabetic macular oedema (DME) refractory to conventional argon macular laser therapy. METHODS: A prospective, consecutive, and noncomparative case series was undertaken involving 38 eyes of 38 patients with refractory DME. Triamcinolone acetonide (4 mg) in 0.1 ml was injected intravitreally. LogMar visual acuity (VA) and macular thickness measured by ocular coherence tomography (OCT) were assessed preoperatively and postoperatively at 1, 3, and 6 months. RESULTS: All patients completed 6 months of follow up. VA (mean+\\/-SD) improved from 0.905+\\/-0.23 to 0.605+\\/-0.28, 0.555+\\/-0.29, and 0.730+\\/-0.30 at 1, 3, and 6 months, respectively. Macular thickness baseline (mean+\\/-SD) on OCT was 418.7+\\/-104.2 microm and this decreased to 276.9+\\/-72.6 microm, 250.6+\\/-53.1 microm, and 308.8+\\/-87.3 microm at 1, 3, and 6 months, respectively. CONCLUSIONS: IVTA may be a potential temporary treatment for refractory DME. It is effective in decreasing macular thickness and improving VA but the effect lasts approximately for 6 months in the majority of patients. Further investigations are required to establish the safety of IVTA for the treatment of DME.

  11. Single intravitreal ranibizumab for myopic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Shatriah I

    2011-08-01

    Full Text Available Saidin Nor-Masniwati, Ismail Shatriah, Embong ZunainaDepartment of Ophthalmology, Universiti Sains Malaysia, Kelantan, MalaysiaAbstract: We report a case of myopic choroidal neovascularization that showed improvement after a single injection of ranibizumab. A 45-year-old Chinese man with high myopia presented with sudden onset painless central scotoma of his right eye of 2 weeks’ duration. There was no history of trauma. His right eye vision on presentation was 6/30 which showed no improvement with pinhole. The right fundus showed myopic maculopathy at the posterior pole with subretinal hemorrhage at the inferotemporal fovea. The optic disc was tilted with inferotemporal peripapillary atrophy. There was a myopic maculopathy appearance in the macula of the left eye. Fundus fluorescein angiography revealed choroidal neovascularization at the fovea of the right eye. A diagnosis of right eye choroidal neovascularization secondary to myopic maculopathy was made. A single intravitreal injection of ranibizumab 0.05 mL was given. Ten weeks following intravitreal injection, vision had improved to 6/7.5, and repeated fundus fluorescein angiography showed absence of choroidal neovascularization. Follow-up at 6 months showed visual acuity had normalized to 6/6 with glasses, which was maintained up to 12 months following treatment. The right fundus showed no further subretinal hemorrhage with no new lesions.Keywords: myopia, choroidal neovascularization, antivascular endothelial growth factor

  12. Anesthetic effectiveness of topical levobupivacaine 0.75% versus topical proparacaine 0.5% for intravitreal injections

    Directory of Open Access Journals (Sweden)

    Nurgül Örnek

    2014-01-01

    Full Text Available Background and Purpose: Today no method of topical anesthesia for intravitreal injection administration has been proven to make the patient comfortable yet. We compared the efficacy of topical levobupivacaine 0.75% and proparacaine 0.5% in patients undergoing intravitreal injections. Materials and Methods: A prospective, randomized study comparing two agents for topical anesthesia in intravitreal injections. Ninety-six consecutive patients were enrolled into two groups to receive either topical levobupivacaine 0.75% (n=48 or proparacaine 0.5% (n=48. Patients were asked to score their pain using a visual analog scale (VAS immediately following the injection. The average of these scores was used as the primary outcome. The surgeon performing the procedure scored his perception of the patients′ pain using the Wong-Baker FACES scale. Results: Mean VAS pain scores for two groups were found to be 44.77 ± 16.42 and 34.18 ± 14.83, respectively. Mean VAS pain score in the proparacaine group was significantly lower than that in the levobupivacaine group (P= 0.003. Mean Wong-Baker FACES scores for the two groups were 1.08 ± 0.49 and 1.10 ± 0.30, respectively. There was no statistically significant difference between levobupivacaine and proparacaine groups (P=0.824. Conclusions: Topical proparacaine 0.5% was more effective in preventing pain during intravitreal injections.

  13. Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection.

    Science.gov (United States)

    Li, Huiling; Palamoor, Mallika; Jablonski, Monica M

    2016-10-01

    Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5 mg/ml and 10 mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.

  14. Impact of the NGF maturation and degradation pathway on the cortical cholinergic system phenotype.

    Science.gov (United States)

    Allard, Simon; Leon, Wanda C; Pakavathkumar, Prateep; Bruno, Martin A; Ribeiro-da-Silva, Alfredo; Cuello, A Claudio

    2012-02-08

    Cortical cholinergic atrophy plays a significant role in the cognitive loss seen with aging and in Alzheimer's disease (AD), but the mechanisms leading to it remain unresolved. Nerve growth factor (NGF) is the neurotrophin responsible for the phenotypic maintenance of basal forebrain cholinergic neurons in the mature and fully differentiated CNS. In consequence, its implication in cholinergic atrophy has been suspected; however, no mechanistic explanation has been provided. We have previously shown that the precursor of NGF (proNGF) is cleaved extracellularly by plasmin to form mature NGF (mNGF) and that mNGF is degraded by matrix metalloproteinase 9. Using cognitive-behavioral tests, Western blotting, and confocal and electron microscopy, this study demonstrates that a pharmacologically induced chronic failure in extracellular NGF maturation leads to a reduction in mNGF levels, proNGF accumulation, cholinergic degeneration, and cognitive impairment in rats. It also shows that inhibiting NGF degradation increases endogenous levels of the mature neurotrophin and increases the density of cortical cholinergic boutons. Together, the data point to a mechanism explaining cholinergic loss in neurodegenerative conditions such as AD and provide a potential therapeutic target for the protection or restoration of this CNS transmitter system in aging and AD.

  15. Effect of Zn(Ⅱ) on the Structure and Biological Activity of Natural β-NGF

    Institute of Scientific and Technical Information of China (English)

    Guang-Hua ZHAO; Ping YU; Xiao-Song HU; Lei ZHAO

    2004-01-01

    Only β-NGF, the subunit of the 7S NGF complex, exhibits NGF activity, but the function ofthe zinc ion in native β-NGF has received little attention. Flameless atomic absorption spectroscopy (FAAS)measurements reveal that native β-NGF contains Zn(II) with a Zn(II)/β-NGF stoichiometry of 1:14.6.The presence of Zn(II) in the native molecule results in significant changes of the secondary structure andlocal tertiary structure around Trp(s) with respect to those of apo β-NGF, as suggested by spectra offluorescence and circular dichrosim. Stopped-flow studies show that there are at least two steps during theinteraction of Zn(I1) with the apo form. In comparison with its apo form, the native β-NGF shows a higherability to trigger the proliferation of TF 1 cells and mediate the survival of PC 12. Thus it is most likely that thestructural changes caused by the presence of Zn(II) directly lead to the increase in the biological activity ofβ-NGF. All results indicate that Zn(II) in native β-NGF plays an important role in the structure and thebiological activity of the protein.

  16. Improving internal environment of mouse uteri with adenomyosis by administration of anti-NGF%抗神经生长因子抗体用于改善子宫腺肌病小鼠宫腔内环境的研究

    Institute of Scientific and Technical Information of China (English)

    李雁; 叶瑶; 徐步芳; 张爱军

    2015-01-01

    目的:探讨抗神经生长因子抗体(anti-NGF)对改善子宫腺肌病(AM)小鼠宫腔内环境的作用.方法:将15只雌性ICR小鼠随机分为AM治疗组(A组)、AM溶剂对照组(B组)及正常对照组(C组),A、B组使用口服他莫昔芬法建立AM小鼠模型.A组小鼠腹腔注射anti-NGF,B组以等体积的生理盐水替代,C组不作任何处理.3组小鼠于动情前期处死取双子宫称量后检测缓激肽受体1(BKR-1)、神经激肽1受体(NK-1R)、同源框基因转录因子A10(HOXA10)及芳香化酶(aromatase)基因与蛋白的表达.结果:A组子宫相对重量同B组,且均明显高于C组(P<0.05);A组BKR-1基因及蛋白和NK-1R基因水平较B组明显降低(P<0.05),与C组比较无统计学差异(P>0.05);A组HOXA10基因及蛋白水平较B组明显增高(P<0.05),与C组比较无统计学差异(P>0.05);A组芳香化酶基因及蛋白水平较B组减低(P<0.05),但仍高于C组(P<0.05).结论:anti-NGF可显著缓解AM模型小鼠子宫炎症,改善内膜容受性、抑制芳香化酶表达,但短期使用不能抑制病灶增殖.

  17. Intravesical NGF Antisense Therapy Using Lipid Nanoparticle for Interstitial Cystitis

    Science.gov (United States)

    2016-12-01

    Testing involved nociceptive behavior testing for pain, cytometry for frequency (ICI), immunohistochemistry, and polymerase chain reaction for NGF...treatment o Pain behavior/bladder over-activity assessment  Tissue Analysis o PCR /ELISA o Patch Clamp Complete animal studies Animal study...hypertrophy seen in H2O2-induced cystitis rats; however these histological changes were alleviated by the LP-11 treatment. (3) In RT- PCR , H2O2-induced

  18. Sensory impairment in mental retardation: a potential role for NGF.

    Science.gov (United States)

    Battaglia, Anna

    2011-06-01

    Sensory impairment is defined as the inability to interpret outside stimuli such as visual, auditory, verbal, sense of touch, taste or smell or feelings of pain. This leads to absence of sensation and neuronal coordination. The impairment may be caused by ageing and other physiological changes, accident or injuries or can be found in some cases of mental retardation (MR) also referred to as intellectual disability. Known cases of MR involving inability to accurately interpret an outside source or stimuli are: Fragile-X syndrome; Tuberous sclerosis complex (TSC) with associated autism spectrum disorder (ASD); Rett syndrome; Autism and ASD with or without MR; Chromosome 22q13.3 deletion syndrome; familial dysautonomia, Prader-Willi's syndrome, Williams syndrome. In this review we will discuss in particular form of ASD and altered sensory sensitivity. The role of NGF in causing pronociceptive activity and its role in peripheral sensitisation is discussed under the light of its involvement in forms of MR where loss of pain perception is a main feature due to mutations to NGF receptors or NGF genes during development. Other forms of MR with altered sensory impairment will be considered as well as additional potential mechanisms involved.

  19. Successful treatment of pseudophakic cystoid macular edema with intravitreal bevacizumab.

    Science.gov (United States)

    Barone, Antonio; Prascina, Francesco; Russo, Vincenzo; Iaculli, Cristiana; Primavera, Vito; Querques, Giuseppe; Stella, Andrea; Delle Noci, Nicola

    2008-07-01

    A 67-year-old woman developed refractory pseudophakic cystoid macular edema (CME) after uneventful phacoemulsification. Three months after an intravitreal injection of bevacizumab (1.25 mg), the CME was completely resolved, with resultant improvement in visual acuity.

  20. Dexamethasone intravitreal implant in the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Dugel PU

    2015-07-01

    Full Text Available Pravin U Dugel,1,2 Francesco Bandello,3 Anat Loewenstein4 1Retinal Consultants of Arizona, Phoenix, AZ, 2Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 3Department of Ophthalmology, University Vita-Salute Scientific Institute San Raffaele, Milan, Italy; 4Department of Ophthalmology, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Diabetic macular edema (DME resembles a chronic, low-grade inflammatory reaction, and is characterized by blood–retinal barrier (BRB breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048 from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%. Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of

  1. Scleral melt following Retisert intravitreal fluocinolone implant

    Directory of Open Access Journals (Sweden)

    Georgalas I

    2014-11-01

    Full Text Available Ilias Georgalas,1 Chrysanthi Koutsandrea,1 Dimitrios Papaconstantinou,1 Dimitrios Mpouritis,1 Petros Petrou1,2 1Ophthalmology Department, University of Athens, Athens, Greece; 2Moorfields Eye Hospital, London, UKAbstract: Intravitreal fluocinolone acetonide implant (Retisert has a high potency, a low solubility, and a very short duration of action in the systemic circulation, enabling the steroid pellet to be small and reducing the risk of systemic side effects. Scleral melt has not been reported as a possible complication of Retisert implant. The authors describe the occurrence of scleral melt 18 months after the implantation of fluocinolone acetonide implant in a 42-year-old Caucasian woman. To the authors’ knowledge, this is the first report of this possible complication.Keywords: Retisert, scleral melt, complication, surgical management

  2. Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases.

    Science.gov (United States)

    Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

    2012-09-03

    This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement.

  3. In vitro Bioeompatibility Assessment of a Novel PRGD/PDLLA/NGF Composite Material

    Institute of Scientific and Technical Information of China (English)

    YIN Yixia; YAN Qiongjiao; YAN Yuhua; CHEN Xiaoming; LI Shipu

    2011-01-01

    The objective of this study was to evaluate the degradability and biocompatibility of a novel composite materials which was grafted with RGD and immobilized with NGF(PRGD/PDLLA/NGF).The releasing of NGF,the biodegradability and cell-biocompatibility of PRGD/PDLLA/NGF membrane were evaluated in vitro.The experimental results showed that the NGF release process was prolonged over 30 days.Furthermore,the PRGD/PDLLA/NGF showed a better hydrophilicity,better biodegradation properties and cells affinity than PDLLA,which means a good support to adhesion and proliferate of Schwann cells.Therefore,the novel composite material holds considerable promise as scaffolds in nerve tissue engineering.

  4. Collagen scaffolds loaded with collagen-binding NGF-beta accelerate ulcer healing.

    Science.gov (United States)

    Sun, Wenjie; Lin, Hang; Chen, Bing; Zhao, Wenxue; Zhao, Yannan; Xiao, Zhifeng; Dai, Jianwu

    2010-03-01

    Studies have shown that exogenous nerve growth factor (NGF) accelerates ulcer healing, but the inefficient growth factor delivery system limits its clinical application. In this report, we found that the native human NGF-beta fused with a collagen-binding domain (CBD) could form a collagen-based NGF targeting delivery system, and the CBD-fused NGF-beta could bind to collagen membranes efficiently. Using the rabbit dermal ischemic ulcer model, we have found that this targeting delivery system maintains a higher concentration and stronger bioactivity of NGF-beta on the collagen membranes by promoting peripheral nerve growth. Furthermore, it enhances the rate of ulcer healing through accelerating the re-epithelialization of dermal ulcer wounds and the formation of capillary lumens within the newly formed tissue area. Thus, collagen membranes loaded with collagen-targeting human NGF-beta accelerate ulcer healing efficiently.

  5. Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2001-02-23

    Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

  6. Ultrasound biomicroscopy study of vitreous incarceration subsequent to intravitreal injections.

    Science.gov (United States)

    Hodjatjalali, Kamran; Riazi, Mohammad; Faghihi, Hooshang; Khorami, Azita

    2012-02-01

    To study the existence of vitreous incarceration by ultrasound biomicroscopy (UBM) at the pars plana after direct intravitreal injection of triamcinolone acetonide ± bevacizumab without anterior chamber paracentesis. Interventional case series. Patients undergoing intravitreal injection of triamcinolone acetonide with or without intravitreal bevacizumab. In 21 eyes, the existence of vitreous incarceration at the pars plana site of intravitreal injection of 0.05 mL of drug was studied by UBM (50 MHz probe of the VUmax, Sonomed, NY), the day after surgery, by 1 technician. The reason for injection was diabetic retinopathy in 12 (57.1%) eyes; age-related macular degeneration in 6 (28.6%) eyes; branch retinal vein occlusion in 2 (9.5%) eyes; and choroiditis in 1 eye (4.8%). In 1 eye, only triamcinolone acetonide was injected, and in the other eyes, bevacizumab mixed with triamcinolone acetonide was injected. We studied 21 eyes in 13 patients. Of the subjects, 61.5% were male. The mean age of the patients was 62.2 years. On the day after intravitreal injection of the drug, vitreous incarceration into the pars plana site was detected by UBM in 42.9% of the eyes. Vitreous incarceration exists after intravitreal injection of drug, but its clinical importance is still unknown. Further long-term prospective studies are recommended. Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  7. Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography

    DEFF Research Database (Denmark)

    Nagiel, Aaron; Freund, K Bailey; Spaide, Richard F;

    2013-01-01

    PURPOSE: To demonstrate the mechanism by which retinal pigment epithelium (RPE) tears occur in eyes with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents using spectral-domain optical coherence tomography (OCT......). DESIGN: Retrospective observational case series. METHODS: OCT images of 8 eyes that developed RPE tears following the administration of intravitreal anti-VEGF agents for neovascular AMD were evaluated. Pretear and posttear images were compared in order to elucidate the mechanism by which RPE tears occur...... to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution...

  8. NGF message and protein distribution in the injured rat spinal cord.

    Science.gov (United States)

    Brown, Arthur; Ricci, Mary-Jo; Weaver, Lynne C

    2004-07-01

    Nerve growth factor (NGF) content of the spinal cord is increased after cord injury. NGF can cause central sprouting of sensory fibers after spinal cord injury (SCI), leading to autonomic dysfunction and pain. NGF also can promote the death of oligodendroglia after SCI. Knowing the source of intraspinal NGF would benefit strategies for minimizing abnormal plasticity and cell death after SCI. We identified these sources, using RNA in situ hybridization to detect NGF mRNA and double-labeling immunocytochemistry for NGF and cell-marking antigens. In uninjured and sham-injured rats, we identified NGF mRNA in leptomeningeal cells and in neurons in the intermediate grey matter, whereas NGF protein was observed only in leptomeningeal cells. At 3-7 days after transection or clip-compression SCI, NGF mRNA and protein were expressed in the lesion and throughout the intermediate grey matter and white matter rostral and caudal to the injury site. Transection-SCI was used to permit comparisons to previous studies; clip-compression injury was used as a more clinically relevant model. mRNA and protein in adjacent sections were expressed in ramified microglia, astrocytes, intermediate grey neurons, pial cells, and leptomeningeal and Schwann cells in the lateral white matter and the lesion site. Rounded macrophages in the lesion were immunoreactive (Ir) for NGF, but the cells expressing NGF mRNA were not in the same areas of the lesion and were not stained by a macrophage marker. Our data demonstrate that glia, neurons, meningeal cells and Schwann cells but not macrophages contribute to the increased intraspinal NGF after SCI.

  9. Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury.

    Science.gov (United States)

    Zhao, Ying-Zheng; Jiang, Xi; Xiao, Jian; Lin, Qian; Yu, Wen-Ze; Tian, Fu-Rong; Mao, Kai-Li; Yang, Wei; Wong, Ho Lun; Lu, Cui-Tao

    2016-01-01

    Nerve growth factor (NGF) has potential in spinal cord injury (SCI) therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Novel heparin-poloxamer (HP) thermo-sensitive hydrogel was constructed to enhance the NGF regeneration on SCI. NGF-HP thermo-sensitive hydrogel was prepared and related characteristics including gelation temperature, rheological behavior and micromorphology were measured. Local NGF delivery to the injured spinal cord was achieved by in situ injection in the injured space. The cellular uptake of NGF-HP hydrogel was evaluated with PC12 cells in vitro. Pathologic characteristics and neuron regeneration effects on the SCI rats were studied to evaluate the enhanced therapy of NGF-HP hydrogel. Endoplasmic reticulum (ER) stress-induced apoptosis was analyzed to explore the related mechanism in SCI regeneration. NGF-HP hydrogel showed good morphology and stable bioactivity of NGF in vitro. NGF-HP hydrogel combined treatment significantly enhanced the efficiency of NGF cellular uptake (Pregeneration. Spinal cord injury (SCI) is a devastating condition that can lead to sudden loss of sensory and autonomic function. Current treatment includes decompression surgery, injury stabilization, secondary complications prevention and rehabilitation. However, neurological recovery is limited. Nerve growth factor (NGF) has potential in SCI therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Hydrogels have good affinity and compatibility to biological tissue. In this study, we developed a novel heparin-poloxamer (HP) thermo-sensitive hydrogel to enhance the spinal cord regeneration of NGF. From SCI rat experiment, HP hydrogel combined with orthotopic injection technique showed best neuroprotective effects among experimental groups. This novel combined technique will provide an effective strategy for SCI regeneration. Copyright © 2015 Acta

  10. NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration.

    Science.gov (United States)

    Zhang, Lei; Wang, Huaxi; Yang, Yan; Liu, Hui; Zhang, Qihao; Xiang, Qi; Ge, Renshan; Su, Zhijian; Huang, Yadong

    2013-06-28

    Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful information for developing new potential therapies for PADAM (Partial Androgen Deficiency in the Aging Male). Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Dexamethasone intravitreal implant in the treatment of diabetic macular edema.

    Science.gov (United States)

    Dugel, Pravin U; Bandello, Francesco; Loewenstein, Anat

    2015-01-01

    Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood-retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ≥25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (implant offers a

  12. Retinal breaks due to intravitreal ocriplasmin

    Directory of Open Access Journals (Sweden)

    Silva RA

    2014-08-01

    Full Text Available Ruwan A Silva, Darius M Moshfeghi, Theodore Leng Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, CA, USA Abstract: Ocriplasmin represents a new treatment option for numerous vitreoretinopathies involving an abnormal vitreomacular interface. While the drug may circumvent the traditional risks of surgical treatment, pharmacologic vitreolysis is not devoid of risk itself. This report presents two cases, one of vitreomacular traction syndrome and the other of a full-thickness macular hole, both of which were treated with an intravitreal injection of ocriplasmin. Notably, in both cases, vitreomacular traction of the macula appears to have been alleviated; however, failure to completely relieve vitreoretinal traction from the peripheral retina generated retinal breaks with one patient eventually developing a macula-involving retinal detachment. Thus, even in instances of ‘successful’ pharmacologic treatment of vitreomacular traction, continued follow-up evaluation is essential. Keywords: posterior vitreous detachment, retinal detachment, vitreomacular traction, ocriplasmin, retinal break, macular hole, laser retinopexy

  13. Effect of NGF on the motility and acrosome reaction of golden hamster spermatozoa in vitro.

    Science.gov (United States)

    Jin, WanZhu; Tanaka, Akane; Watanabe, Gen; Matsuda, Hiroshi; Taya, Kazuyoshi

    2010-08-01

    Motility and fertilizing ability are known to be two important physiological attributes of a mature sperm, yet the mechanism by which spermatozoa mature and become motile remains largely unknown. It has been shown that nerve growth factor (NGF) is a protein essential for the development, maintenance and survival of the peripheral and central nervous systems. However, the presence of high levels of NGF protein and mRNA do not correlate with the innervations by NGF sensitive fibers in tissues such as the testis, prostate and seminal vesicles. These observations have shifted the attention of research to the role of NGF outside of the nervous system. Here, we demonstrate that NGF and its receptors TrkA and p75 are widely expressed in the testis, accessory reproductive organ, and the epididymal sperms. We also show that NGF stimulates two important aspects of sperm functions, motility and the acrosome reaction, in a time- and dose-dependent manner. NGF activated the sperm cell acrosome reaction, while addition of inhibitors specific for MAPK kinase significantly blocked the sperm acrosome reaction. Taken together, our findings suggest that NGF plays an integral role in sperm motility and the acrosome reaction through, at least in part, the MAPK signalling pathway.

  14. Axial blanket for 16NGF Angra 1 fuel type

    Energy Technology Data Exchange (ETDEWEB)

    Sadde, Luciano Martins; Faria, Eduardo Fernandes [Industrias Nucleares do Brasil (INB), Resende, RJ (Brazil)]. E-mails: sadde@inb.gov.br; faria@inb.gov.br; Sang-Keun You [Korea Nuclear Fuel Co. Ltd. (KNFC), Taejon (Korea, Republic of)]. E-mail: skyou@knfc.co.kr

    2007-07-01

    Angra-1, Kori-2 and Krsko are nuclear power plants with the same design. However, the fuel assemblies have some differences in design due to the countries strategies and the differences in the fabrication process. The 16NGF (16x16 Next Generation Fuel) was developed by INB, KNFC and Westinghouse in order to be used in these three nuclear power plants and the 'Axial Blanket' is one of the new features for the 16NGF design. The main purpose of the Axial Blanket Optimization study is to determine which axial blanket enrichment and length would provide the better fuel cycle cost benefit. All of the calculations were performed using Gadolinium as Burnable Absorber and solid pellets type for Axial Blanket. The results indicate 1.8 w/o U235 enrichment and 8 inches length as the best option of Axial Blanket from the fuel cycle cost benefit standpoint. The economy is about 1.8%. The difference in the reload cost in the range between 1.5 and 2.6 w/o U235 enrichment and for the 6 and 8 inches length is not so significant. Due that, from the Fq limit standpoint and also for longer cycle length requirements, a higher axial blanket enrichment (2.6 w/o) and shorter length (6 inches) is recommended. (author)

  15. NGF/TrkA Signaling as a Therapeutic Target for Pain.

    Science.gov (United States)

    Hirose, Munetaka; Kuroda, Yoshihiro; Murata, Eri

    2016-02-01

    Nerve growth factor (NGF) was first discovered approximately 60 years ago by Rita Levi-Montalcini as a protein that induces the growth of nerves. It is now known that NGF is also associated with Alzheimer's disease and intractable pain, and hence, it, along with its high-affinity receptor, tropomyosin receptor kinase (Trk) A, is considered to be 1 of the new targets for therapies being developed to treat these diseases. Anti-NGF antibody and TrkA inhibitors are known drugs that suppress NGF/TrkA signaling, and many drugs of these classes have been developed thus far. Interestingly, local anesthetics also possess TrkA inhibitory effects. This manuscript describes the development of an analgesic that suppresses NGF/TrkA signaling, which is anticipated to be 1 of the new methods to treat intractable pain.

  16. MiR-21 is an Ngf-modulated microRNA that supports Ngf signaling and regulates neuronal degeneration in PC12 cells.

    Science.gov (United States)

    Montalban, Enrica; Mattugini, Nicola; Ciarapica, Roberta; Provenzano, Claudia; Savino, Mauro; Scagnoli, Fiorella; Prosperini, Gianluca; Carissimi, Claudia; Fulci, Valerio; Matrone, Carmela; Calissano, Pietro; Nasi, Sergio

    2014-06-01

    The neurotrophins Ngf, Bdnf, NT-3, NT4-5 have key roles in development, survival, and plasticity of neuronal cells. Their action involves broad gene expression changes at the level of transcription and translation. MicroRNAs (miRs)-small RNA molecules that control gene expression post-transcriptionally-are increasingly implicated in regulating development and plasticity of neural cells. Using PC12 cells as a model system, we show that Ngf modulates changes in expression of a variety of microRNAs, including miRs known to be modulated by neurotrophins-such as the miR-212/132 cluster-and several others, such as miR-21, miR-29c, miR-30c, miR-93, miR-103, miR-207, miR-691, and miR-709. Pathway analysis indicates that Ngf-modulated miRs may regulate many protein components of signaling pathways involved in neuronal development and disease. In particular, we show that miR-21 enhances neurotrophin signaling and controls neuronal differentiation induced by Ngf. Notably, in a situation mimicking neurodegeneration-differentiated neurons deprived of Ngf-this microRNA is able to preserve the neurite network and to support viability of the neurons. These findings uncover a broad role of microRNAs in regulating neurotrophin signaling and suggest that aberrant expression of one or more Ngf-modulated miRs may be involved in neurodegenerative diseases.

  17. Traumatic chorioretinal folds treated with intra-vitreal triamcinolone injection

    Directory of Open Access Journals (Sweden)

    Kook Young Kim

    2013-01-01

    Full Text Available A 34-year-old male visited the hospital due to decreased visual acuity in the left eye following an injury from a car accident. In the left eye, best-corrected visual acuity (BCVA was hand motion and intraocular pressure (IOP was 8 mmHg. Choroidal vasodilation and chorioretinal folds were observed by spectral domain-optical coherence tomography (SD-OCT. Topical and systemic steroid treatments did not improve the chorioretinal folds. Twelve months after the injury, intra-vitreal triamcinolone (4 mg/0.1 ml was injected. Six months after intra-vitreal triamcinolone injection, BCVA in the left eye had improved to 20/100. Fundus examination showed improvement in retinal vascular tortuosity and SD-OCT revealed improvements in choroidal vasodilation and chorioretinal folds. Intra-vitreal triamcinolone injection (IVTI was effective against traumatic chorioretinal folds with no recurrence based on objective observation by fundus photography and SD-OCT.

  18. Intravitreal injection of perfluoropropane for the treatment of vitreomacular traction

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    Xiao-Ping Wan

    2013-07-01

    Full Text Available AIM: To study the efficacy of a single intravitreal injection of perfluoropropane(C3F8in releasing vitreomacular traction. METHODS: Twelve eyes of 12 consecutive patients with vitreomacular traction received a single intravitreal injection of 0.3mL 100%(C3F8were retrospectively analyzed. The best corrected vision acuity and the neural epithelium thickness of central macular were observed. RESULTS: One month following treatment, vitreomacular traction was released in 5 eyes(42%, mean final visual acuity(VAimproved 0.04 and mean central foveal thickness decreased by 69μm. The vision acuity before and after treatment were 0.20±0.07, 0.25±0.04 respectively.CONCLUSION: Intravitreal C3F8 injection could offer a minimally invasive alternative to pars plana vitrectomy in patients with vitreomacular traction.

  19. Management of noninfectious posterior uveitis with intravitreal drug therapy

    Science.gov (United States)

    Tan, Hui Yi; Agarwal, Aniruddha; Lee, Cecilia S; Chhablani, Jay; Gupta, Vishali; Khatri, Manoj; Nirmal, Jayabalan; Pavesio, Carlos; Agrawal, Rupesh

    2016-01-01

    Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis).

  20. Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer's disease.

    Science.gov (United States)

    Iulita, M Florencia; Bistué Millón, M Beatriz; Pentz, Rowan; Aguilar, Lisi Flores; Do Carmo, Sonia; Allard, Simon; Michalski, Bernadeta; Wilson, Edward N; Ducatenzeiler, Adriana; Bruno, Martin A; Fahnestock, Margaret; Cuello, A Claudio

    2017-09-01

    Evidence from human neuropathological studies indicates that the levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are compromised in Alzheimer's disease. However, the causes and temporal (pathology-dependent) evolution of these alterations are not completely understood. To elucidate these issues, we investigated the McGill-R-Thy1-APP transgenic rat, which exhibits progressive intracellular and extracellular amyloid-beta (Aβ) pathology and ensuing cognitive deficits. Neurochemical analyses revealed a differential dysregulation of NGF and BDNF transcripts and protein expression. While BDNF mRNA levels were significantly reduced at very early stages of amyloid pathology, before plaques appeared, there were no changes in NGF mRNA expression even at advanced stages. Paradoxically, the protein levels of the NGF precursor were increased. These changes in neurotrophin expression are identical to those seen during the progression of Alzheimer's disease. At advanced pathological stages, deficits in the protease cascade controlling the maturation and degradation of NGF were evident in McGill transgenic rats, in line with the paradoxical upregulation of proNGF, as seen in Alzheimer's disease, in the absence of changes in NGF mRNA. The compromise in NGF metabolism and BDNF levels was accompanied by downregulation of cortical cholinergic synapses; strengthening the evidence that neurotrophin dysregulation affects cholinergic synapses and synaptic plasticity. Our findings suggest a differential temporal deregulation of NGF and BDNF neurotrophins, whereby deficits in BDNF mRNA appear at early stages of intraneuronal Aβ pathology, before alterations in NGF metabolism and cholinergic synapse loss manifest. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effects of autoimmune NGF deprivation in the adult rabbit and offspring.

    Science.gov (United States)

    Johnson, E M; Gorin, P D; Osborne, P A; Rydel, R E; Pearson, J

    1982-05-20

    An experimental autoimmune approach to the production of nerve growth factor deprivation, which we have previously described in the rat and guinea pig, has been applied to the rabbit. This species was chosen for study because of several potential advantages. The rabbit produces large litters and has a relatively short gestation period. More importantly, rabbits generate high titers of antibody against mouse NGF and large amounts of maternal antibody are passively transferred to the developing rabbit fetus compared to most other species, particularly the rat. The sympathetic nervous system of adult rabbit immunized against mouse NGF underwent degeneration with up to an 85% decrease in neuronal numbers in the superior cervical ganglion after 10 months of immunization, thus providing further evidence that NGF is required for the survival of mature sympathetic neurons. Despite the fact that newborn rabbits born to anti-NGF producing mothers had much higher titers of anti-NGF than did rats, the effects on the developing sympathetic and sensory nervous systems were not found to be any greater than in rats. Reductions in norepinephrine levels in the heart and spleen of adult rabbits born to anti-NGF producing mothers were greater than in small intestine. Prenatal exposure to maternal anti-NGF caused reductions (up to 70%) in the number of neurons in the dorsal root ganglia. Substance-P immunoreactivity was reduced in the substantia gelatinosa of the spinal cord of rabbit exposed to maternal anti-NGF. These changes, however, were not greater than seen in the rat. We conclude that although the rabbits offers some advantage in the study of the effects of NGF deprivation in the adult animal, it appears less well suited than the rat or guinea pig to the study of the effects of NGF deprivation on development.

  2. Management of noninfectious posterior uveitis with intravitreal drug therapy

    Directory of Open Access Journals (Sweden)

    Tan HY

    2016-10-01

    Full Text Available Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis. Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis

  3. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant

    Directory of Open Access Journals (Sweden)

    Giannaccare G

    2016-07-01

    Full Text Available Giuseppe Giannaccare, Michela Fresina, Alberto Pazzaglia, Piera Versura Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES, Alma Mater Studiorum University of Bologna, Sant’Orsola‑Malpighi Teaching Hospital, Bologna, Italy Abstract: Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month

  4. Intravitreal methotrexate infusion for proliferative vitreoretinopathy

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    Sadaka A

    2016-09-01

    Full Text Available Ama Sadaka,1 Robert A Sisk,1–3 James M Osher,1,3 Okan Toygar,4 Melinda K Duncan,5 Christopher D Riemann1,3 1Department of Ophthalmology, University of Cincinnati College of Medicine, 2Department of Opthalmology, Cincinnati Children’s Hospital Medical Center, 3Cincinnati Eye Institute, Cincinnati, OH, USA; 4Department of Ophthalmology, Bahcesehir University Medical Faculty, Istanbul, Turkey; 5Department of Biological Sciences, University of Delaware, Newark, DE, USA Purpose: The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI during pars plana vitrectomy (PPV for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR.Methods: Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review.Results: Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22 or a history of severe inflammation associated with high PVR risk (n=7 received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66% and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%. At the last follow-up examination, the retinas of 26 of 29 eyes (90% remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10% developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months.Conclusion: Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series. Keywords: tractional retinal detachment, recurrent retinal detachment, pars

  5. Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

    Science.gov (United States)

    Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

    2014-01-01

    Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

  6. Intravitreal moxifloxacin in the management of Ochrobactrum intermedium endophthalmitis due to metallic intraocular foreign body

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    Jacobs DJ

    2013-08-01

    Full Text Available David J Jacobs,1,2 Thomas J Grube,3 Harry W Flynn Jr,4 Craig M Greven,5 Avinash Pathengay,6 Darlene Miller,4 Robert F Sanke,1,2 Joseph Thorman7 1Trinity Regional Eyecare, Minot, ND, USA; 2School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA; 3Grube Retina Clinic, Mandan, ND, USA; 4Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA; 5Department of Ophthalmology, Wake Forest University Eye Center, Winston-Salem, NC, USA; 6LV Prasad Eye Institute, Hyderabad, India; 7Rolla Eye Clinic, ND, USA Abstract: A healthy 34-year-old man presented with Ochrobactrum intermedium endophthalmitis due to a metallic intraocular foreign body. After vitrectomy, lensectomy, removal of the metallic intraocular foreign body, intravitreal vancomycin and ceftazidime, and systemic ciprofloxacin, intraocular inflammation worsened. Repeat vitreous culture confirmed persistent endophthalmitis due to multidrug-resistant O. intermedium. The endophthalmitis successfully resolved after the administration of intravitreal moxifloxacin. Keywords: moxifloxacin, Ochrobactrum intermedium, endophthalmitis, intraocular foreign body

  7. Safety evaluation of poly(lactic-co-glycolic acid/poly(lactic-acid microspheres through intravitreal injection in rabbits

    Directory of Open Access Journals (Sweden)

    Rong XF

    2014-06-01

    Full Text Available Xianfang Rong,1 Weien Yuan,2 Yi Lu,1 Xiaofen Mo11Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaAbstract: Poly(lactic-co-glycolic acid (PLGA and/or poly(lactic-acid (PLA microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled

  8. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

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    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  9. Management of macular epiretinal membrane by vitrectomy and intravitreal triamcinolone

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    Dhananjay Shukla

    2014-01-01

    Full Text Available A patient underwent successful vitrectomy for macular epiretinal membrane with anatomical and functional improvement. 10 weeks later, there was a recurrence of macular edema with corresponding visual decline. An intravitreal injection of triamcinolone acetonide not only restored the macular anatomy but also improved the visual outcome beyond that achieved after surgery.

  10. Successful Resolution of Preretinal Haemorrhage with Intravitreal Ranibizumab

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    Baharuddin Noorlaila

    2016-01-01

    Full Text Available We would like to report two cases of preretinal haemorrhage from two different aetiology courses of bleeding being treated with intravitreal ranibizumab and its outcome. Our first case was a 39-year-old man with a diagnosis of severe aplastic anaemia that presented with bilateral premacular haemorrhages in both eyes. His right eye vision was 6/45 and it was counting finger in the left eye. He was treated with intravitreal ranibizumab once to the right eye and twice to the left eye. Right eye showed complete resolution of premacular haemorrhage and minimal residual premacular haemorrhage in the left eye at 3 months after initial presentation. Our second case was a 32-year-old healthy teacher that presented with preretinal haemorrhage at superotemporal region extending to macular area in left eye secondary to valsalva retinopathy. Her left vision was counting finger. She was treated with single intravitreal ranibizumab to the left eye. There was significant reduction of premacular haemorrhage and her left eye vision improved to 6/6 at 10 weeks after injection. Both cases had favourable outcome with intravitreal ranibizumab and can be considered as nonsurgical treatment option in treating premacular haemorrhage.

  11. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

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    Orozco-Hernández A

    2014-09-01

    Full Text Available Axel Orozco-Hernández,1 Ximena Ortega-Larrocea,1 Gustavo Sánchez-Bermúdez,1 Gerardo García-Aguirre,1 Virgilio Morales Cantón,1 Raul Velez-Montoya2 1Retina Department, Asociación para Evitar la Ceguera en México IAP, Mexico City, Mexico; 2Department of Ophthalmology, University of Colorado School of Medicine, Rocky Mountain Lions Eye Institute, Aurora, CO, USA Background: Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods: This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results: Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were

  12. Intravitreal Bevacizumab (Avastin Injection for Neovascular Glaucoma

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    Shahin Yazdani

    2008-12-01

    Full Text Available

    PURPOSE: To report two cases with neovascular glaucoma secondary to ischemic central retinal vein occlusion (CRVO who were treated with intravitreal bevacizumab. CASE REPORT: Two patients were referred for neovascular glaucoma following CRVO. Visual acuity was light perception. Both eyes had extensive iris neovascularization (NVI, synechial angle closure and high intraocular pressure (IOP in spite of anti-glaucoma medications. After obtaining informed consent, both eye received an intravitreal injection of 2.5 mg (0.1 ml bevacizumab (Avastin. Both eyes demonstrated dramatic IOP reduction together with decreased severity and extent of NVI during 4 weeks of follow up. Visual acuity remained unchanged. CONCLUSION: Despite the dramatic short-term response in terms of IOP reduction and regression of neovascularization, due to limited clinical experience, one should consider this novel indication for bevacizumab cautiously.

  1. Acute retinal necrosis following intravitreal dexamethasone (Ozurdex® implant

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    Murat Kucukevcilioglu

    2015-04-01

    Full Text Available A 52-year-old woman undergoing azathioprine treatment for rheumatoid arthritis developed acute retinal necrosis a month after intravitreal dexamethasone (Ozurdex ® implantation for posterior uveitis in the left eye. Varicella zoster virus (VZV DNA was detected in the anterior chamber and vitreous samples on polymerase chain reaction (PCR analysis. Retinal detachment occurred despite systemic and intravitreal antiviral therapy. Favorable structural and functional outcomes were achieved after retinal surgery with silicone oil. To the authors’ knowledge, this is the first reported case of acute retinal necrosis following placement of an Ozurdex® implant. Physicians practicing Ozurdex® implantations should be aware of this unusual but devastating complication. Extra caution and frequent follow-up are required in all immunocompromised patients receiving Ozurdex® implantation.

  2. Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells.

    Science.gov (United States)

    Fukuda, Yu; Fukui, Takao; Hikichi, Chika; Ishikawa, Tomomasa; Murate, Kenichiro; Adachi, Takeshi; Imai, Hideki; Fukuhara, Koki; Ueda, Akihiro; Kaplan, Allen P; Mutoh, Tatsuro

    2015-01-30

    Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin(®)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction.

  3. Treatment of noninfectious posterior uveitis with dexamethasone intravitreal implant

    Directory of Open Access Journals (Sweden)

    Jane S Myung

    2010-12-01

    Full Text Available Jane S Myung, Grant D Aaker, Szilárd KissDepartment of Ophthalmology, Weill Cornell Medical Center, New York, NY, USAPurpose: To report our experience with dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA in noninfectious posterior uveitis.Methods: A retrospective chart review of patients with noninfectious uveitis treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed. Complete ophthalmic examination including signs of inflammatory activity, visual acuity, fundus photography, fluorescein angiography, optical coherence tomography, and tolerability of the implant were assessed.Results: Six eyes of 4 consecutive patients treated with a total of 8 dexamethasone 0.7 mg sustained-release intravitreal implants for posterior noninfectious uveitis were included. Two patients presented with unilateral idiopathic posterior uveitis; 2 patients had bilateral posterior uveitis, one secondary to sarcoidosis and the other to Vogt-Koyanagi-Harada syndrome. All eyes showed clinical and angiographic evidence of decreased inflammation following implant placement. Mean follow-up time post-injection was 5.25 months. Four eyes received 1 and 2 eyes received 2 Ozurdex implants during the follow-up period. The duration of effect of the implant was 3 to 4 months. No serious ocular or systemic adverse events were noted during the follow-up period.Conclusions: In patients with noninfectious posterior uveitis, sustained-release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option for controlling intraocular inflammation.Keywords: corticosteroids, dexamethasone implant, Ozurdex, uveitis

  4. Selective Gene Transfer to the Retina Using Intravitreal Ultrasound Irradiation

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    Shozo Sonoda

    2012-01-01

    Full Text Available This paper aims to evaluate the efficacy of intravitreal ultrasound (US irradiation for green fluorescent protein (GFP plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 μL and bubble liposomes (BLs; 50 μL was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM of GFP-positive cells (32±4.9; n=7; P<0.01 . No GFP-positive cells were observed in the control eyes (n=7. Intravitreal retinal US irradiation can transfer the GFP plasmid into the retina without causing any apparent damage. This procedure could be used to transfer genes and drugs directly to the retina and therefore has potential therapeutic value.

  5. Intravitreal ranibizumab as adjuvant treatment for neovascular glaucoma

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    Flavia Gazze Ticly

    2013-04-01

    Full Text Available The purpose of this study was to describe a prospective case series of 5 eyes treated with intravitreal ranibizumab injection for neovascular glaucoma (NVG. Five patients with clinically uncontrolled NVG secondary to proliferative diabetic retinopathy (4 patients and central retinal vein occlusion (1 patient, non-responsive to maximal tolerable medication and panretinal photocoagulation, received intravitreal ranibizumab injection (0.5 mg. Patients were seen at 1st, 3rd and 7th day after the ranibizumab injection and when it was necessary. Success was defined as intraocular pressure (IOP 21, despite maximal tolerable medication, underwent trabeculectomy with 0.5mg/ml mitomycin C (MMC for 1 minute. Failure was defined as IOP > 21 mmHg, phthisis bulbi, loss of light perception or additional glaucoma surgery. The primary outcome was 6-month IOP control. Mean IOP before the ranibizumab injection was 37 mmHg (7 mmHg SD. Two out of five eyes underwent only ranibizumab injection, having an IOP control after the procedure. Three patients were submitted to trabeculectomy with MMC on the 7th day after the injection. At 6-month follow-up, the mean IOP was 12mmHg (3 mmHg SD. All eyes showed regression of rubeosis iridis and IOP control. Visual acuity improved in 2 eyes worsened in 1 eye, and remained stable in 2 eyes. These data suggest that intravitreal ranibizumab injection may be a useful tool in the treatment of NVG.

  6. Decreased serum level of NGF in alcohol-dependent patients with declined executive function

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    Bae H

    2014-11-01

    Full Text Available Hwallip Bae,1 Youngsun Ra,1 Changwoo Han,2 Dai-Jin Kim3 1Department of Psychiatry, Myongji Hospital, Goyang, 2Department of Psychiatry, Keyo Hospital, Uiwang, 3Department of Psychiatry, Seoul St Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea Abstract: The role of neurotrophic factors has been highlighted as a cause of decline in the cognitive function of alcohol-dependent patients. It is known that nerve-growth factor (NGF, one of the neurotrophins, is related to the growth and differentiation of nerve cells, as well as to a decline in cognitive function. The purpose of this study was to investigate the relationship between decreased NGF levels and cognitive decline in alcohol-dependent patients. The serum concentration of NGF was measured in 38 patients with chronic alcohol dependence, and several neuropsychological tests were also performed for cognitive function assessment. The results indicated a significant correlation between serum NGF level and the trail-making test part B, which evaluates executive function, but did not show a significant correlation with other cognitive function tests. An increased serum level of NGF was associated with a decreased completion time in the trail-making test B, and this finding indicates that a high serum level of NGF is related to greater executive function. This finding may imply a protective role of NGF in preventing neuron damage among patients with alcohol dependence. Larger controlled studies will be necessary in the future to investigate this issue further. Keywords: nerve-growth factor, alcohol dependence, executive function, trail-making test

  7. Activation of CB1 inhibits NGF-induced sensitization of TRPV1 in adult mouse afferent neurons.

    Science.gov (United States)

    Wang, Z-Y; McDowell, T; Wang, P; Alvarez, R; Gomez, T; Bjorling, D E

    2014-09-26

    Transient receptor potential vanilloid 1 (TRPV1)-containing afferent neurons convey nociceptive signals and play an essential role in pain sensation. Exposure to nerve growth factor (NGF) rapidly increases TRPV1 activity (sensitization). In the present study, we investigated whether treatment with the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced sensitization of TRPV1 in adult mouse dorsal root ganglion (DRG) afferent neurons. We found that CB1, NGF receptor tyrosine kinase A (trkA), and TRPV1 are present in cultured adult mouse small- to medium-sized afferent neurons and treatment with NGF (100ng/ml) for 30 min significantly increased the number of neurons that responded to capsaicin (as indicated by increased intracellular Ca(2 +) concentration). Pretreatment with the CB1 agonist ACEA (10nM) inhibited the NGF-induced response, and this effect of ACEA was reversed by a selective CB1 antagonist. Further, pretreatment with ACEA inhibited NGF-induced phosphorylation of AKT. Blocking PI3 kinase activity also attenuated the NGF-induced increase in the number of neurons that responded to capsaicin. Our results indicate that the analgesic effect of CB1 activation may in part be due to inhibition of NGF-induced sensitization of TRPV1 and also that the effect of CB1 activation is at least partly mediated by attenuation of NGF-induced increased PI3 signaling.

  8. [Construction of recombinant human nerve growth factor (rh-β-NGF) eukaryotic vector and its expression in HEK293 cells].

    Science.gov (United States)

    Li, Jingchuan; Xue, Bofu; Yuan, Yuan; Ma, Mo; Zhu, Lin; Milburn, Rebecca; Le, Li; Hu, Peizhen; Ye, Jing

    2015-03-01

    Human nerve growth factor (NGF) is a nerve cell growth regulation factor, which can provide nutrition for the neurons and promote the neurites outgrowth. In order to produce large-scale recombinant human nerve growth factor (rh-beta-NGF), we constructed a plasmid vector, which can stably express the rh-beta-NGF in the HEK293 cell lines. First, the plasmid of pCMV-beta-NGF-IRES-dhfr was constructed and transformed into HEK293 cells. Then MTX pressurized filter and limiting dilution methods were used to obtain monoclonal HEK293 cell lines. After stepwise reducing serum in culture media, the cells eventually adapted to serum-free medium and secreted rh-beta-NGF. SDS-PAGE analysis revealed that the expression product owned a molecular weight of about 13 kDa and a purity of more than 50%. The peptide mapping sequencing analysis demonstrated the sequences of rh-beta-NGF matched with the theoretical ones. Later we purified this protein by ion exchange and molecular sieve chromatograph. Finally, our experimental results exhibited that the recombinant cell lines can stably express rh-beta-NGF with a high efficiency of more than 20 pg/cell x day. In addition, this protein could successfully induce differentiation of PC12 cells. In summary, our recombinant HEK293 cells can express bio-active rh-beta-NGF with great efficiency and stability, which supply a valid basis to large-scale production of rh-beta-NGF.

  9. Effect of Zn(Ⅱ) on the Structure and Biological Activity of Natural β-NGF

    Institute of Scientific and Technical Information of China (English)

    Guang-HuaZHAO; PingYU; Xiao-SongHU; LeiZHAO

    2004-01-01

    Only β-NGF, the subunit of the 7S NGF complex, exhibits NGF activity, but the function ofthe zinc ion in native β-NGF has received little attention. Flameless atomic absorption spectroscopy (FAAS)measurements reveal that native β-NGF contains Zn(Ⅱ) with a Zn(Ⅱ)/β-NGF stoichiometry of 1 : 14.6.The presence of Zn(Ⅱ) in the native molecule results in significant changes of the secondary structure andlocal tertiary structure around Trp(s) with respect to those of apo β-NGF, as suggested by spectra offluorescence and circular dichrosim. Stopped-flow studies show that there are at least two steps during theinteraction of Zn(Ⅱ) with the apo form. In comparison with its apo form, the native β-NGF shows a higherability to trigger the proliferation of TF1 cells and mediate the survival of PC 12. Thus it is most likely that thestructural changes caused by the presence of Zn(II) directly lead to the increase in the biological activity of β-NGE All results indicate that Zn(Ⅱ) in native β-NGF plays an important role in the structure and thebiological activity of the protein.

  10. Three intravitreal bevacizumab versus two intravitreal triamcinolone injections in recent onset central retinal vein occlusion.

    Science.gov (United States)

    Ramezani, Alireza; Esfandiari, Hamed; Entezari, Morteza; Moradian, Siamak; Soheilian, Masoud; Dehsarvi, Babak; Yaseri, Mehdi

    2014-11-01

    To evaluate the effects of repeated intravitreal injections of bevacizumab (IVB) versus triamcinolone acetonide (IVT) in the treatment of acute central retinal vein occlusion (CRVO). In this randomized clinical trial, 86 eyes with recent onset (central macular thickness (CMT), and intraocular pressure (IOP) changes. Mean BCVA improved significantly at 6 months in both groups; from 0.87 ± 0.49 to 0.41 ± 0.35 logMAR in IVB group, and from 0.81 ± 0.45 to 0.62 ± 0.48 logMAR in IVT group (p < 0.001). However, between-group differences reach a significant level at months 4 (p = 0.003) and 6 (p < 0.001) in favour of the IVB group. In terms of CMT reduction, the difference between the groups was statistically significant (p = 0.002) at month 6. Significant differences were noted more in the ischaemic cases in favour of the IVB group. Mean IOP rise was significantly higher in the IVT group at all visits. Both 3-times monthly IVB injections and 2-times IVT injections could be effective in cases with recent onset CRVO up to 6 months. However, considering the better outcomes after IVB injections and the potential complications of IVT injections, we would recommend prescheduled repeated IVB injections for such cases. The observed favourable responses were more pronounced in the ischaemic types; nevertheless, this should be confirmed in larger studies. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Effects of NGF-induced muscle sensitization on proprioception and nociception.

    Science.gov (United States)

    Svensson, Peter; Wang, Kelun; Arendt-Nielsen, Lars; Cairns, Brian E

    2008-07-01

    Temporomandibular disorders (TMDs) are associated with perturbation of proprioceptive and nociceptive function. Recent studies have shown that injection of the neurotrophic protein nerve growth factor (NGF) into the masseter muscle causes sensitization to mechanical pressure stimuli; however, it is not clear if vibration sense and jaw stretch reflexes as measures of proprioceptive function as well as glutamate-evoked pain are also altered. We tested the hypothesis that NGF-induced mechanical sensitization would be associated with changes in vibration sense and stretch reflex sensitivity as well as facilitation of glutamate-evoked pain responses. A double-blind, randomized and placebo-controlled study was conducted on 14 healthy men. In one session subjects received an injection of NGF (5 microg in 0.2 ml) into the masseter muscle and in a control session an injection of buffered isotonic saline (0.9%, 0.2 ml). Subjects assessed their pain intensity on a 0-10 cm visual analogue scale (VAS) for 15 min after the injections. Pressure pain thresholds (PPT), vibration sense and jaw stretch reflexes were recorded at baseline and 1, 2, 3 and 24 h post-injection. The sensitivity to injections of glutamate into the masseter muscle (1 M, 0.2 ml) was assessed after 24 h. ANOVAs were used to assess significant differences. NGF did not cause more pain than isotonic saline, but significantly reduced PPTs 1, 2, 3 and 24 h post-injection (P affected by the NGF-induced sensitization; however, after glutamate injection a significant increase in the stretch reflex was observed in the injected masseter muscle in both sessions (P = 0.002). There were no significant differences in the perceived pain intensity of the glutamate injection between the masseter muscle pretreated with NGF or control (P > 0.414), although the glutamate-evoked pain drawing areas were larger for the NGF-pretreated masseter muscle (P = 0.009). In conclusion, this study confirms that masseter muscle injection of

  12. NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome.

    Science.gov (United States)

    Chaldakov, G N; Fiore, M; Stankulov, I S; Hristova, M; Antonelli, A; Manni, L; Ghenev, P I; Angelucci, F; Aloe, L

    2001-10-01

    While multiple growth factor, cytokines, and immune cells are identified in atherosclerotic lesions, as well as an essential nonneuronal function of neurotrophins implicated in cardiovascular tissue development and in lipid and glucose metabolism, the role of the neurotrophins NGF and BDNF and also the adipokine leptin in human coronary atherosclerosis and related disorders, such as metabolic syndrome, remains unclear. Here we report that (i) both the amount and the immunoreactivity of NGF was reduced and the expression of p75NGF receptor and the number of mast cell increased in human atherosclerotic coronary arteries (n = 12) compared with control specimens (n = 9) obtained from autopsy cases, and (ii) NGF and BDNF plasma levels were reduced in patients with metabolic syndrome (n = 23) compared with control subjects (n = 10). Also, in metabolic syndrome patients, a positive correlation between the plasma leptin levels and the number of adipose tissue mast cells was found, suggesting that leptin may be a novel adipoimmune mediator. Altogether, the results provide the first correlative evidence for the potential involvement of NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome, implying neuroimmune and adipoimmune pathways in the pathobiology of these cardiovascular disorders.

  13. Optical coherence tomography and vessel diameter changes after intravitreal bevacizumab in diabetic macular oedema

    DEFF Research Database (Denmark)

    Soliman, W.; Vinten, M.; Sander, B.

    2008-01-01

    Purpose: To assess the effect of intravitreal bevacizumab on diabetic macular oedema (DMO) and retinal vessel calibres. Methods: We performed a consecutive case series study in which 10 consecutive eyes with diffuse DMO, two of which had not previously been treated, received an intravitreal injec...

  14. Short-term efficacy of intravitreal dobesilate in central serous chorioretinopathy

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    Cuevas Pedro

    2012-07-01

    Full Text Available Abstract Purpose To report the anatomic and functional outcome of intravitreal dobesilate to treat recurrent central serous chorioretinopathy (CSC. Methods This is an interventional case report in which dobesilate was intravitreally injected in a case of recurrent CSC. Main measures included fundoscopy, Snellen visual acuity (VA testing, fluorescein angiography and optical coherence tomography (OCT. Results We present anatomical and functional evidences, obtained as early as eleven days after the treatment, of the efficacy of intravitreal dobesilate, in the treatment of chronic CSC condition. The effect after intravitreal dobesilate injection for CSC might be related to the normalization of retinal architecture. Conclusions Intravitreal dobesilate may be an effective treatment option for recurrent CSC.

  15. Rita Levi-Montalcini and the discovery of NGF, the first nerve cell growth factor.

    Science.gov (United States)

    Aloe, Luigi

    2011-06-01

    The nerve growth factor (NGF) is a signaling protein, discovered by Rita Levi-Montalcini in the early 1950's for its effect on growth and differentiation of specific populations of neurons of the peripheral nervous system. Originally identified as neurite outgrowth-stimulating factor, later studies revealed that the purified molecule has a number of target cells in the central nervous system and on nonneuronal cells. Moreover, recent studies showed the potential therapeutic properties of NGF in neuropathies of the central and peripheral nervous system and diseases of the eye and skin. Here I briefly describe the discovery of NGF, the early studies of Rita LeviMontalcini, a pioneer in modern neuroscience, and my scientific and human experience working in her laboratory for over 40 years.

  16. NGF controls APP cleavage by downregulating APP phosphorylation at Thr668: relevance for Alzheimer's disease.

    Science.gov (United States)

    Triaca, Viviana; Sposato, Valentina; Bolasco, Giulia; Ciotti, Maria Teresa; Pelicci, Piergiuseppe; Bruni, Amalia C; Cupidi, Chiara; Maletta, Raffaele; Feligioni, Marco; Nisticò, Robert; Canu, Nadia; Calissano, Pietro

    2016-08-01

    NGF has been implicated in forebrain neuroprotection from amyloidogenesis and Alzheimer's disease (AD). However, the underlying molecular mechanisms are still poorly understood. Here, we investigated the role of NGF signalling in the metabolism of amyloid precursor protein (APP) in forebrain neurons using primary cultures of septal neurons and acute septo-hippocampal brain slices. In this study, we show that NGF controls the basal level of APP phosphorylation at Thr668 (T668) by downregulating the activity of the Ser/Thr kinase JNK(p54) through the Tyr kinase signalling adaptor SH2-containing sequence C (ShcC). We also found that the specific NGF receptor, Tyr kinase A (TrkA), which is known to bind to APP, fails to interact with the fraction of APP molecules phosphorylated at T668 (APP(pT668) ). Accordingly, the amount of TrkA bound to APP is significantly reduced in the hippocampus of ShcC KO mice and of patients with AD in which elevated APP(pT668) levels are detected. NGF promotes TrkA binding to APP and APP trafficking to the Golgi, where APP-BACE interaction is hindered, finally resulting in reduced generation of sAPPβ, CTFβ and amyloid-beta (1-42). These results demonstrate that NGF signalling directly controls basal APP phosphorylation, subcellular localization and BACE cleavage, and pave the way for novel approaches specifically targeting ShcC signalling and/or the APP-TrkA interaction in AD therapy.

  17. Characterization of NGF, trkANGFR, and p75NTR in Retina of Mice Lacking Reelin Glycoprotein

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    Bijorn Omar Balzamino

    2014-01-01

    Full Text Available Both Reelin and Nerve Growth Factor (NGF exert crucial roles in retinal development. Retinogenesis is severely impaired in E-reeler mice, a model of Reelin deficiency showing specific Green Fluorescent Protein expression in Rod Bipolar Cells (RBCs. Since no data are available on Reelin and NGF cross-talk, NGF and trkANGFR/ p75NTR expression was investigated in retinas from E-reeler versus control mice, by confocal microscopy, Western blotting, and real time PCR analysis. A scattered increase of NGF protein was observed in the Ganglion Cell Layer and more pronounced in the Inner Nuclear Layer (INL. A selective increase of p75NTR was detected in most of RBCs and in other cell subtypes of INL. On the contrary, a slight trend towards a decrease was detected for trkANGFR, albeit not significant. Confocal data were validated by Western blot and real time PCR. Finally, the decreased trkANGFR/ p75NTR ratio, representative of p75NTR increase, significantly correlated with E-reeler versus E-control. These data indicate that NGF-trkANGFR/ p75NTR is affected in E-reeler retina and that p75NTR might represent the main NGF receptor involved in the process. This first NGF-trkANGFR/ p75NTR characterization suggests that E-reeler might be suitable for exploring Reelin-NGF cross-talk, representing an additional information source in those pathologies characterized by retinal degeneration.

  18. Expression of nerve growth factor (NGF, TrkA and p75NTR in developing human foetal teeth

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    Thimios A. Mitsiadis

    2016-08-01

    Full Text Available Nerve growth factor (NGF is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively p75NTR and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75NTR and TrkA proteins during human foetal tooth development, in order to better understand the mode of NGF signalling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibres that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localised in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75NTR expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75NTR in foetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well conserved during evolution. The expression patterns of NGF, p75NTR and TrkA during odontogenesis suggest regulatory roles for NGF signalling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibres within dental tissues.

  19. NGF promotes hemodynamic recovery in a rabbit hindlimb ischemic model through trkA- and VEGFR2-dependent pathways.

    Science.gov (United States)

    Karatzas, Andreas; Katsanos, Konstantinos; Lilis, Ioannis; Papadaki, Helen; Kitrou, Panagiotis; Lecht, Shimon; Marcinkiewicz, Cezary; Siablis, Dimitris; Lelkes, Peter I; Lazarovici, Philip; Tsopanoglou, Nikos E

    2013-09-01

    Nerve growth factor (NGF) has been reported to play an important role in physiological and pathological angiogenesis. Based on these observations, we hypothesized that NGF may induce the formation of functional blood vessels in a hindlimb ischemic rabbit model. Hindlimb ischemia was induced in 34 rabbits bilaterally by endovascular embolization of femoral arteries. On the 7th, 14th, and 20th postembolization days, NGF was injected intramuscularly, in 1 ischemic limb, and vehicle was injected in the contralateral control limb. On the 40th day, newly developed collateral vessels (diameter >500 μm) were quantified by transauricular intraarterial subtraction angiography. Perfusion analysis of an in vivo dynamic computed tomography study was performed to the limbs to investigate the hemodynamic recovery of the distal ischemic tissues. Functional estimation of limb perfusion showed a statistically significant increase of blood flow and blood volume for NGF. However, the increase of the collateral vessels was not detectable angiographically, providing evidence for the existence of a NGF-stimulated capillary angiogenic network but not increase of arteriogenesis. The combination of NGF with either tropomyosin-related kinase type A or vascular endothelial growth factor receptor 2 antagonists abolished the NGF-induced hemodynamic recovery. These findings provide new insights into understanding the involvement of NGF in vascular formation and its applications in therapeutic angiogenesis.

  20. Expression of Nerve Growth Factor (NGF), TrkA, and p75NTR in Developing Human Fetal Teeth

    Science.gov (United States)

    Mitsiadis, Thimios A.; Pagella, Pierfrancesco

    2016-01-01

    Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75NTR and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75NTR, and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75NTR expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75NTR in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75NTR, and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues. PMID:27536251

  1. Pars Plana Vitrectomy and Intravitreal Phacoemulsification for Dropped Nuclei

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    Khalil Ghasemi Falavarjani

    2012-01-01

    Full Text Available Purpose: To report the outcomes of pars plana vitrectomy (PPV and intravitreal phacoemulsification in patients with dropped nuclei/nuclear fragments following complicated cataract surgery. Methods: In this retrospective case series, charts of patients who had undergone PPV and intravitreal phacoemulsification for removal of dislocated nuclei/lens fragments were reviewed. After standard PPV, a conventional phacoemulsification probe with an amputated sleeve was used for grasping and emulsifying the nucleus/nuclear fragments in mid/anterior vitreous cavity. Pre- and postoperative visual acuity, and intra- and postoperative complications were recorded. Results: A total of 22 patients with mean age of 71.1΁8.2 years were studied. Mean interval between complicated cataract surgery and PPV was 26.6΁36.5 (range: 0-120 days. Patients were followed for a mean of 105.5΁57.5 days. Preoperatively, best corrected visual acuity was 2.4΁0.6 logMAR which was improved to 1.4΁0.6 logMAR at final follow-up (P<0.001. Intraoperative complications included iatrogenic peripheral retinal breaks in three eyes. Postoperative complications consisted of epiretinal membrane formation in one eye, hypotony in one eye, and medically-controlled glaucoma in 2 eyes. Conclusion: In this series, PPV and intravitreal phacoemulsification using a conventional phacoemulsification probe in patients with dropped nuclei/nuclear fragments following complicated cataract surgery resulted in visual improvement without any complications directly attributable to the probe.

  2. Topical azithromycin or ofloxacin for endophthalmitis prophylaxis after intravitreal injection

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    Romero-Aroca P

    2012-10-01

    Full Text Available Pedro Romero-Aroca,1 Laura Sararols,2 Lluis Arias,3 Ricardo P Casaroli-Marano,4 Francisca Bassaganyas51Department of Ophthalmology, Hospital Universitari Sant Joan, Universidad Rovira i Virgili, Reus, 2Department of Ophthalmology, Hospital de Granollers, Granollers, 3Department of Ophthalmology, Hospital Universitari de Bellvitge, Barcelona, 4Instituto Clínico de Oftalmologia, Hospital Clínic de Barcelona, Barcelona, 5Department of Ophthalmology, Hospital de la Sant Creu i Sant Pau, Barcelona, SpainBackground: The number of patients who have undergone intravitreal injections has increased enormously in recent years, but a consensus is still lacking on prophylaxis for endophthalmitis. The aim of this prospective, observational study was to evaluate the prophylactic effect of azithromycin eye drops versus ofloxacin eye drops.Methods: The study was conducted in five hospitals in Spain and included all patients undergoing intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib over one year. Patients received azithromycin 15 mg/g eye drops (twice daily on the day prior to injection and for another 2 days or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days.Results: In the azithromycin group, there were 4045 injections in 972 eyes of 701 patients. In the ofloxacin group, there were 4151 injections in 944 eyes of 682 patients. There were two cases of endophthalmitis (0.049% in the azithromycin group and five (0.12% in the ofloxacin group. The odds ratio of presenting with endophthalmitis in the ofloxacin group compared with the azithromycin group was 2.37 (95% confidence interval [CI] 1.32–3.72, P < 0.001. There were two cases of noninfectious uveitis after triamcinolone injection in the azithromycin group (0.049% and two (0.048% in the ofloxacin group; no significant differences were observed (odds ratio 0.902, 95% CI 0.622–1.407, P = 0.407. Conjunctival hyperemia was

  3. Immediate effect of intravitreal injection of bevacizumab on intraocular pressure

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    Lemos-Reis R

    2014-07-01

    Full Text Available Ricardo Lemos-Reis,1 Nuno Moreira-Gonçalves,1 António B Melo,1 Ângela M Carneiro,1,2 Fernando M Falcão-Reis1,2 1Department of Ophthalmology of Hospital de São João, Porto, Portugal; 2Department of Sense Organs, Faculty of Medicine, University of Porto, Porto, Portugal Purpose: To investigate the immediate effect of intravitreal injection of bevacizumab on intraocular pressure (IOP. Methods: This was a prospective and nonrandomized study. A total of 291 eyes with macular edema or active choroidal neovascularization were submitted to a single 1.25 mg (0.05 mL bevacizumab intravitreal injection. Intraocular pressure was measured with an Icare® tonometer immediately before and after injection in a seated position. The presence of subconjunctival reflux was recorded. The fellow eye served as the control.Results: Mean preoperative IOP was 18.0±5.9 mmHg in the treated eye versus 16.9±6.0 mmHg in the fellow eye. Mean postoperative IOP was 42.1±14.5 mmHg in the treated eye versus 17.5±6.0 mmHg in the fellow eye. The IOP variation was statistically significant in both cases and controls (P<0.001 and P=0.003, respectively, and this increase was higher in cases than in controls (P<0.001. Postoperative IOPs higher than 50 mmHg were achieved in 32.0% of the eyes. Subconjunctival reflux was present in 21.3% and determined a lower IOP rise (P<0.001. Tested variables (glaucoma, phakic status, and sex did not have a statistically significant effect on IOP rise or subconjunctival reflux. Conclusion: IOP increases with intravitreal bevacizumab injection, reaching 50 mmHg or more in about one third of patients. A higher IOP is expected if no subconjunctival reflux occurs. The baseline IOP does not influence the incidence of subconjunctival reflux. The clinical relevance of these facts has yet to be clarified. Keywords: bevacizumab, intraocular pressure, intravitreal injection, Icare®

  4. Nerve growth factor (NGF)-mediated regulation of p75(NTR) expression contributes to chemotherapeutic resistance in triple negative breast cancer cells.

    Science.gov (United States)

    Chakravarthy, Reka; Mnich, Katarzyna; Gorman, Adrienne M

    2016-09-30

    Triple negative breast cancer [TNBC] cells are reported to secrete the neurotrophin nerve growth factor [NGF] and express its receptors, p75 neurotrophin receptor [p75(NTR)] and TrkA, leading to NGF-activated pro-survival autocrine signaling. This provides a rationale for NGF as a potential therapeutic target for TNBC. Here we show that exposure of TNBC cells to NGF leads to increased levels of p75(NTR), which was diminished by NGF-neutralizing antibody or NGF inhibitors [Ro 08-2750 and Y1086]. NGF-mediated increase in p75(NTR) levels were partly due to increased transcription and partly due to inhibition of proteolytic processing of p75(NTR). In contrast, proNGF caused a decrease in p75(NTR) levels. Functionally, NGF-induced increase in p75(NTR) caused a decrease in the sensitivity of TNBC cells to apoptosis induction. In contrast, knock-down of p75(NTR) using shRNA or small molecule inhibition of NGF-p75(NTR) interaction [using Ro 08-2750] sensitized TNBC cells to drug-induced apoptosis. In patient samples, the expression of NGF and NGFR [the p75(NTR) gene] mRNA are positively correlated in several subtypes of breast cancer, including basal-like breast cancer. Together these data suggest a positive feedback loop through which NGF-mediated upregulation of p75(NTR) can contribute to the chemo-resistance of TNBC cells.

  5. Intracerebroventricular Administration of Nerve Growth Factor Induces Gliogenesis in Sensory Ganglia, Dorsal Root, and within the Dorsal Root Entry Zone

    OpenAIRE

    Schlachetzki, Johannes C.M.; Pizzo, Donald P.; Debbi A. Morrissette; Jürgen Winkler

    2015-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia...

  6. Intravitreal gas injection for the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    McHugh D

    2011-10-01

    Full Text Available Dominic McHugh, Bhaskar Gupta, Manzar Saeed King's College Hospital, Denmark Hill, London, England, UK Purpose: This study investigates the efficacy of an intravitreal gas injection in inducing a posterior vitreous detachment (PVD in patients with clinically significant diabetic macular edema refractory to laser therapy. Methods: A local ethics committee-approved technique of an intravitreal injection of pure perfluoropropane gas (C3F8 was performed for all participants. After a period of prone positioning, the patients underwent regular and detailed clinical review. Main outcome measures: The induction of a PVD, change in macular thickness, change in visual acuity. Results: A PVD was induced in all five eyes with subsequent signs of reduction in macular thickness and resolution of exudates. Mean visual improvement was 11 ETDRS (Early Treatment Diabetic Retinopathy Study letters (range 4–21. Apart from a transient vitreous hemorrhage in one eye, there were no significant treatment-related complications. Conclusion: The induction of a PVD by pneumatic retinopexy appears to have a significant influence on diabetic macular edema in eyes which have not successfully responded to macular laser therapy. A randomized clinical trial is justified on the basis of the initial promising data. Keywords: optical coherence tomography, OCT, posterior vitreous detachment, perfluoropropane

  7. Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF signaling and survival

    Science.gov (United States)

    Harrington, Anthony W.; Hillaire, Coryse St.; Zweifel, Larry S.; Glebova, Natalia O.; Philippidou, Polyxeni; Halegoua, Simon; Ginty, David D.

    2012-01-01

    Summary NGF and NT3 collaborate to support development of sympathetic neurons. Although both neurotrophins activate TrkA-dependent axonal extension, NGF is unique in its ability to promote retrograde transport of TrkA endosomes and retrograde survival. Here, we report that actin depolymerization is essential for initiation of NGF/TrkA endosome trafficking and that a Rac1–cofilin signaling module associated with TrkA early endosomes supports their maturation to retrograde transport-competent endosomes. Moreover, the actin-regulatory endosomal components are absent from NT3-formed TrkA endosomes, explaining the failure of NT3 to support retrograde TrkA transport and survival. The inability of NT3 to activate Rac1-GTP–cofilin signaling is likely due to the labile nature of NT3/TrkA complexes within the acidic environment of TrkA early endosomes. Thus, TrkA endosomes associate with actin-modulatory proteins to promote F-actin disassembly enabling their maturation into transport-competent signaling endosomes. Differential control of this process explains how NGF in final targets, but not NT3 from intermediate targets, supports retrograde survival of sympathetic neurons. PMID:21816277

  8. Interleukin-1β and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes

    Directory of Open Access Journals (Sweden)

    Patte Christine

    2006-04-01

    Full Text Available Abstract C3a and C5a anaphylatoxins are proinflammatory polypeptides released during complement activation. They exert their biological activities through interaction with two G protein-coupled receptors named C3aR and C5aR, respectively. In the brain, these receptors are expressed on glial cells, and some recent data have suggested that anaphylatoxins could mediate neuroprotection. In this study, we used RT-PCR and ribonuclease protection assays (RPA to investigate the role of anaphylatoxins on neurotrophin expression by the human glioblastoma cell line T98G and by rat astrocytes. Our data show that for both cell types, anaphylatoxins upregulate expression of NGF mRNA. This response depended on a G protein-coupled pathway since pre-treatment of cells with pertussis toxin (PTX completely blocked NGF mRNA increases. This effect was anaphylatoxin-specific since pre-incubation with anti-C3a or anti-C5aR antibodies abolished the effects of C3a and C5a, respectively. The regulation of NGF mRNA by anaphylatoxins was not accompanied by translation into protein expression, but there was a significant synergic effect of anaphylatoxins/IL-1b costimulation. Our demonstration of involvement of anaphylatoxins in the NGF release process by astrocytes suggests that C3a and C5a could modulate neuronal survival in the CNS.

  9. Creating Well-Being: Increased Creativity and proNGF Decrease following Quadrato Motor Training.

    Science.gov (United States)

    Venditti, Sabrina; Verdone, Loredana; Pesce, Caterina; Tocci, Nicoletta; Caserta, Micaela; Ben-Soussan, Tal Dotan

    2015-01-01

    Mind-body practices (MBP) are known to induce electrophysiological and morphological changes, whereas reports related to changes of neurotrophins are surprisingly scarce. Consequently, in the current paper, we focused on the Quadrato motor training (QMT), a newly developed whole-body movement-based MBP, which has been reported to enhance creativity. Here we report the effects of 4 weeks of daily QMT on creativity and proNGF level in two interrelated studies. In Study A, we examined the effects of QMT compared with a walking training (WT) in healthy adults, utilizing the alternate uses task. In contrast with the WT, QMT resulted in increased creativity. In addition, the change in creativity negatively correlated with the change in proNGF levels. In Study B, we examined QMT effects on creativity and additional metacognitive functions in children, using a nonintervention group as control. Similar to Study A, following QMT, we found a negative correlation of proNGF with creativity, as well as working memory updating and planning ability. Together, the current results point to the relationship between increased creativity and decreased proNGF following MBP. Thus, the current research emphasizes the importance of widening the scope of examination of "MBP in motion" in relation to metacognition and well-being.

  10. Meta-analysis of mNGF therapy for peripheral nerve injury: a systematic review

    Institute of Scientific and Technical Information of China (English)

    LIU Yan-rong; LIU Qiang

    2012-01-01

    Objective: To assess the efficacy and safety of mouse nerve growth factor (mNGF) in patients with peripheral nerve injury.Methods: Such electronic database as Cochrane Library (Issue 1,2011),Medline (1950-2011),Embase (1980-2011),National Knowledge Infrastructure (1979-2011) were searched and meanwhile relevant journals such as Chinese Journal of Orthopaedics,Chinese Journal of Microsurgery,Chinese Journal ofNeurosurgery,etc were searched as well to collect all randomized controlled trials and quasi-randomized controlled trials of mNGF on patients with peripheral nerve injury.The quality of included studies was assessed according to the criteria recommended by the Cochrane Handbook for Systematic Reviews of Interventions and the data were extracted by two reviewers independently.Metaanalysis was conducted by RevMan 5.1 software.Results: Forty-one studies involving 3 304 patients with peripheral nerve injury were included.The results of meta-analysis showed that:(1) the total effective rate of peripheral nerve injury treatment in mNGF group was obviously higher than that in control group (OR=6.36,95% CI 4.96-8.15,P<0.01); (2) the scores of activities of daily living (ADL) in mNGF group was significantly higher than that in control group (weighted mean difference=l.97,95% CI 1.33-2.61,P<0.01); (3) the incidence of adverse reaction in mNGF group was higher than that in control group,(OR=1.66,95% CI 1.61-2.38,P=0.006),but the adverse effects were mild,which could be relieved without specific treatment or just given symptomatic treatment,and disappeared at the end of treatment.Conclusions: The mNGF therapy is effective for peripheral nerve injury.It can obviously improve patient's ADL.Though the incidence of adverse reaction in mNGF treatment group is higher than that in control group,this does not influence the treatment outcomes.

  11. NGF is an essential survival factor for bronchial epithelial cells during respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Sreekumar Othumpangat

    Full Text Available Overall expression of neurotrophins in the respiratory tract is upregulated in infants infected by the respiratory syncytial virus (RSV, but it is unclear where (structural vs. inflammatory cells, upper vs. lower airways and why, these changes occur. We analyzed systematically the expression of neurotrophic factors and receptors following RSV infection of human nasal, tracheal, and bronchial epithelial cells, and tested the hypothesis that neurotrophins work as innate survival factors for infected respiratory epithelia.Expression of neurotrophic factors (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF and receptors (trkA, trkB, p75 was analyzed at the protein level by immunofluorescence and flow cytometry and at the mRNA level by real-time PCR. Targeted siRNA was utilized to blunt NGF expression, and its effect on virus-induced apoptosis/necrosis was evaluated by flow cytometry following annexin V/7-AAD staining.RSV infection was more efficient in cells from more distal (bronchial vs. more proximal origin. In bronchial cells, RSV infection induced transcript and protein overexpression of NGF and its high-affinity receptor trkA, with concomitant downregulation of the low-affinity p75(NTR. In contrast, tracheal cells exhibited an increase in BDNF, trkA and trkB, and nasal cells increased only trkA. RSV-infected bronchial cells transfected with NGF-specific siRNA exhibited decreased trkA and increased p75(NTR expression. Furthermore, the survival of bronchial epithelial cells was dramatically decreased when their endogenous NGF supply was depleted prior to RSV infection.RSV infection of the distal airway epithelium, but not of the more proximal sections, results in overexpression of NGF and its trkA receptor, while the other p75(NTR receptor is markedly downregulated. This pattern of neurotrophin expression confers protection against virus-induced apoptosis, and its inhibition amplifies programmed cell death in the infected

  12. Intravitreal injections: what do patients prefer? Analysis of patient's satisfaction and preferences about where to perform intravitreal injections.

    Science.gov (United States)

    Rodríguez Ramírez, M; del Barrio Manso, M I; Martín Sánchez, M D

    2014-12-01

    To analyse satisfaction and patient preferences on the location where they receive an intravitreal injection. A survey was conducted with the intention of analysing these patients who attended the macula clinic and have been intervened using an intravitreal injection at least once in the day hospital or in the theatre setting, comparing both locations. The majority of the interviewed patients preferred the day hospital (50.0 versus 37.5%), mostly because of the comfort and the quick service. In patients with severe age-related macular degeneration (AMD) the option is reversed. The overall satisfaction level was positive in both cases (with 87.5% of patients satisfied or very satisfied in the day hospital and 91.1% in the theatre setting). Through the analysis of different aspects of clinical care the assessment was the same or superior for 75.0% of these patients, except in the waiting time. There were no cases of endophthalmitis. In general, patients prefer the clinical intervention in the consulting room than in the theatre setting because of the quicker service. There are several characteristics that can influence this choice and should be taken into account. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  13. Plasticity in developing rat uterine sensory nerves: the role of NGF and TrkA.

    Science.gov (United States)

    Chalar, C; Richeri, A; Viettro, L; Chávez-Genaro, R; Bianchimano, P; Marmol, N M; Crutcher, K; Burnstock, G; Cowen, T; Brauer, M M

    2003-11-01

    In the present study we investigated the effects of infantile/prepubertal chronic oestrogen treatment, chemical sympathectomy with guanethidine and combined sympathectomy and chronic oestrogen treatment on developing sensory nerves of the rat uterus. Changes in sensory innervation were assessed quantitatively on uterine cryostat tissue sections stained for calcitonin gene-related peptide (CGRP). Uterine levels of NGF protein, using immunohistochemistry and ELISA, and mRNA, using Northern blots and in situ hybridization, were also measured. Finally, levels of TrkA NGF receptor in sensory neurons of T13 and L1 dorsal root ganglia (DRG), which supply the uterus, were assessed using densitometric immunohistochemistry. These studies showed that: (1) chronic oestrogen treatment led to an 83% reduction in the intercept density of CGRP-immunoreactive nerves; (2) sympathectomy had no effect on the density of uterine sensory nerves or on the pattern of oestrogen-induced changes; (3) NGF mRNA and protein increased following sympathectomy or chronic oestrogen treatment; and (4) oestrogen produced increased intensity of labelling (28%) for TrkA receptors in small-diameter sensory neurons, but decreased labelling (13%) in medium-sized neurons, which represent the large majority of the DRG neurons supplying the upper part of the uterine horn. Contrary to expectations, increased levels of NGF after sympathectomy and oestrogen treatment did not lead to increased sensory innervation of the uterus. The possibility that alterations in neuronal levels of TrkA contribute to the lack of response of uterine sensory nerves to the oestrogen-induced increase in NGF levels is discussed.

  14. Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF receptors, preventing neuronal apoptosis.

    Directory of Open Access Journals (Sweden)

    Iakovos Lazaridis

    2011-04-01

    Full Text Available The neurosteroid dehydroepiandrosterone (DHEA, produced by neurons and glia, affects multiple processes in the brain, including neuronal survival and neurogenesis during development and in aging. We provide evidence that DHEA interacts with pro-survival TrkA and pro-death p75(NTR membrane receptors of neurotrophin nerve growth factor (NGF, acting as a neurotrophic factor: (1 the anti-apoptotic effects of DHEA were reversed by siRNA against TrkA or by a specific TrkA inhibitor; (2 [(3H]-DHEA binding assays showed that it bound to membranes isolated from HEK293 cells transfected with the cDNAs of TrkA and p75(NTR receptors (K(D: 7.4 ± 1.75 nM and 5.6 ± 0.55 nM, respectively; (3 immobilized DHEA pulled down recombinant and naturally expressed TrkA and p75(NTR receptors; (4 DHEA induced TrkA phosphorylation and NGF receptor-mediated signaling; Shc, Akt, and ERK1/2 kinases down-stream to TrkA receptors and TRAF6, RIP2, and RhoGDI interactors of p75(NTR receptors; and (5 DHEA rescued from apoptosis TrkA receptor positive sensory neurons of dorsal root ganglia in NGF null embryos and compensated NGF in rescuing from apoptosis NGF receptor positive sympathetic neurons of embryonic superior cervical ganglia. Phylogenetic findings on the evolution of neurotrophins, their receptors, and CYP17, the enzyme responsible for DHEA biosynthesis, combined with our data support the hypothesis that DHEA served as a phylogenetically ancient neurotrophic factor.

  15. Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.

    Directory of Open Access Journals (Sweden)

    Fernando C Alsina

    Full Text Available The Sprouty (Spry family of proteins represents endogenous regulators of downstream signaling pathways induced by receptor tyrosine kinases (RTKs. Using real time PCR, we detect a significant increase in the expression of Spry4 mRNA in response to NGF, indicating that Spry4 could modulate intracellular signaling pathways and biological processes induced by NGF and its receptor TrkA. In this work, we demonstrate that overexpression of wild-type Spry4 causes a significant reduction in MAPK and Rac1 activation and neurite outgrowth induced by NGF. At molecular level, our findings indicate that ectopic expression of a mutated form of Spry4 (Y53A, in which a conserved tyrosine residue was replaced, fail to block both TrkA-mediated Erk/MAPK activation and neurite outgrowth induced by NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory effect of Spry4 on NGF signaling. Downregulation of Spry4 using small interference RNA knockdown experiments potentiates PC12 cell differentiation and MAPK activation in response to NGF. Together, these findings establish a new physiological mechanism through which Spry4 regulates neurite outgrowth reducing not only the MAPK pathway but also restricting Rac1 activation in response to NGF.

  16. Differential effects of lidocaine on nerve growth factor (NGF)-evoked heat- and mechanical hyperalgesia in humans.

    Science.gov (United States)

    Weinkauf, B; Obreja, O; Schmelz, M; Rukwied, R

    2012-04-01

    We investigated the effects of a non-specific sodium channel blocker (lidocaine) on heat pain thresholds and mechanical impact pain at day 7 and 21 after intradermal injection of 1 μg NGF. Measurements were performed in 12 healthy male subjects prior to and 5 min after intradermal injection of 150 μl lidocaine administered at concentrations of 0.01% (∼0.4 mM) and 0.1% (∼4 mM) to both NGF and control skin sites. NGF caused a maximum reduction of heat pain thresholds at day 7 (NGF 42.6 ± 0.6 vs. 49.4 ± 0.3 °C in control skin). Lidocaine sensitized normal skin for heat pain, but reduced heat hyperalgesia after NGF at day 7 (44.3 ± 0.8 °C, lidocaine 0.1%; p Lidocaine dose-dependently attenuated mechanically-induced pain at both control and NGF-treated sites. Maximum lidocaine effects on mechanical hyperalgesia were recorded at day 21 in NGF skin (pain reduction to VAS 37 ± 4, p lidocaine 0.1%. Lidocaine differentially affects NGF-induced mechanical hyperalgesia (analgesic effect) and heat sensitivity of nociceptors (sensitizing effect). These opposing responses may be attributed to block of sodium channels vs. sensitization of TRPV1. NGF-evoked extreme mechanical impact pain indicates high action potential discharge frequencies, which might be more susceptible to lidocaine block.

  17. Targeted NGF siRNA delivery attenuates sympathetic nerve sprouting and deteriorates cardiac dysfunction in rats with myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Hesheng Hu

    Full Text Available Nerve growth factor (NGF is involved in nerve sprouting, hyper-innervation, angiogenesis, anti-apoptosis, and preservation of cardiac function after myocardial infarction (MI. Positively modulating NGF expression may represent a novel pharmacological strategy to improve post-infarction prognosis. In this study, lentivirus encoding NGF short interfering RNA (siRNA was prepared, and MI was modeled in the rat using left anterior descending coronary artery ligation. Rats were randomly grouped to receive intramyocardial injection of lentiviral solution containing NGF-siRNA (n = 19, MI-SiNGF group, lentiviral solution containing empty vector (n = 18, MI-GFP group or 0.9% NaCl solution (n = 18, MI-control group, or to receive thoracotomy and pericardiotomy (n = 17, sham-operated group. At 1, 2, 4, and 8 wk after transduction, rats in the MI-control group had higher levels of NGF mRNA and protein than those in the sham-operated group, rats in the MI-GFP group showed similar levels as the MI-control group, and rats in the MI-SiNGF group had lower levels compared to the MI-GFP group, indicating that MI model was successfully established and NGF siRNA effectively inhibited the expression of NGF. At 8 wk, echocardiographic and hemodynamic studies revealed a more severe cardiac dysfunction in the MI-siRNA group compared to the MI-GFP group. Moreover, rats in the MI-siRNA group had lower mRNA and protein expression levels of tyrosine hydroxylase (TH and growth-associated protein 43-positive nerve fibers (GAP-43 at both the infarcted border and within the non-infarcted left ventricles (LV. NGF silencing also reduced the vascular endothelial growth factor (VEGF expression and decreased the arteriolar and capillary densities at the infarcted border compared to the MI-GFP group. Histological analysis indicated a large infarcted size in the MI-SiNGF group. These findings suggested that endogenous NGF silencing attenuated sympathetic nerve sprouting

  18. ProNGF Drives Localized and Cell Selective Parvalbumin Interneuron and Perineuronal Net Depletion in the Dentate Gyrus of Transgenic Mice

    Science.gov (United States)

    Fasulo, Luisa; Brandi, Rossella; Arisi, Ivan; La Regina, Federico; Berretta, Nicola; Capsoni, Simona; D'Onofrio, Mara; Cattaneo, Antonino

    2017-01-01

    ProNGF, the precursor of mature Nerve Growth Factor (NGF), is the most abundant NGF form in the brain and increases markedly in the cortex in Alzheimer's Disease (AD), relative to mature NGF. A large body of evidence shows that the actions of ProNGF and mature NGF are often conflicting, depending on the receptors expressed in target cells. TgproNGF#3 mice, expressing furin-cleavage resistant proNGF in CNS neurons, directly reveal consequences of increased proNGF levels on brain homeostasis. Their phenotype clearly indicates that proNGF can be a driver of neurodegeneration, including severe learning and memory behavioral deficits, cholinergic deficits, and diffuse immunoreactivity for A-beta and A-beta-oligomers. In aged TgproNGF#3 mice spontaneous epileptic-like events are detected in entorhinal cortex-hippocampal slices, suggesting occurrence of excitatory/inhibitory (E/I) imbalance. In this paper, we investigate the molecular events linking increased proNGF levels to the epileptiform activity detected in hippocampal slices. The occurrence of spontaneous epileptiform discharges in the hippocampal network in TgproNGF#3 mice suggests an impaired inhibitory interneuron homeostasis. In the present study, we detect the onset of hippocampal epileptiform events at 1-month of age. Later, we observe a regional- and cellular-selective Parvalbumin interneuron and perineuronal net (PNN) depletion in the dentate gyrus (DG), but not in other hippocampal regions of TgproNGF#3 mice. These results demonstrate that, in the hippocampus, the DG is selectively vulnerable to altered proNGF/NGF signaling. Parvalbumin interneuron depletion is also observed in the amygdala, a region strongly connected to the hippocampus and likewise receiving cholinergic afferences. Transcriptome analysis of TgproNGF#3 hippocampus reveals a proNGF signature with broad down-regulation of transcription. The most affected mRNAs modulated at early times belong to synaptic transmission and plasticity and

  19. ProNGF Drives Localized and Cell Selective Parvalbumin Interneuron and Perineuronal Net Depletion in the Dentate Gyrus of Transgenic Mice.

    Science.gov (United States)

    Fasulo, Luisa; Brandi, Rossella; Arisi, Ivan; La Regina, Federico; Berretta, Nicola; Capsoni, Simona; D'Onofrio, Mara; Cattaneo, Antonino

    2017-01-01

    ProNGF, the precursor of mature Nerve Growth Factor (NGF), is the most abundant NGF form in the brain and increases markedly in the cortex in Alzheimer's Disease (AD), relative to mature NGF. A large body of evidence shows that the actions of ProNGF and mature NGF are often conflicting, depending on the receptors expressed in target cells. TgproNGF#3 mice, expressing furin-cleavage resistant proNGF in CNS neurons, directly reveal consequences of increased proNGF levels on brain homeostasis. Their phenotype clearly indicates that proNGF can be a driver of neurodegeneration, including severe learning and memory behavioral deficits, cholinergic deficits, and diffuse immunoreactivity for A-beta and A-beta-oligomers. In aged TgproNGF#3 mice spontaneous epileptic-like events are detected in entorhinal cortex-hippocampal slices, suggesting occurrence of excitatory/inhibitory (E/I) imbalance. In this paper, we investigate the molecular events linking increased proNGF levels to the epileptiform activity detected in hippocampal slices. The occurrence of spontaneous epileptiform discharges in the hippocampal network in TgproNGF#3 mice suggests an impaired inhibitory interneuron homeostasis. In the present study, we detect the onset of hippocampal epileptiform events at 1-month of age. Later, we observe a regional- and cellular-selective Parvalbumin interneuron and perineuronal net (PNN) depletion in the dentate gyrus (DG), but not in other hippocampal regions of TgproNGF#3 mice. These results demonstrate that, in the hippocampus, the DG is selectively vulnerable to altered proNGF/NGF signaling. Parvalbumin interneuron depletion is also observed in the amygdala, a region strongly connected to the hippocampus and likewise receiving cholinergic afferences. Transcriptome analysis of TgproNGF#3 hippocampus reveals a proNGF signature with broad down-regulation of transcription. The most affected mRNAs modulated at early times belong to synaptic transmission and plasticity and

  20. Efficacy of first Ranibizumab intravitreal injection on macular edema caused by retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Hong Cao

    2015-09-01

    Full Text Available AIM: To observe the efficacy of first Ranibizumab intravitreal injection on macular edema caused by retinal vein occlusion(RVO. METHODS: Thirty-nine eyes of 39 patients with macular edema due to RVO were treated in our hospital during June 2014 to December 2014. Patients received intravitreal injection of 0.05mL ranibizumab. Best corrected visual acuity(BCVA, central macular thickness(CMTand cube average thickness(CATwere analyzed at 2d, 2, and 4wk after injection, respectively. RESULTS: The baseline BCVA(LogMAR, CMT and CAT were 0.82±0. 45, 541±136μm and 382±107μm before treatment. After first ranibizumab intravitreal injection, mean BVCA significantly improved at 2d(0. 56±0.35,PPPPPPPPPCONCLUSION: First intravitreal injection of ranibizumab can improve macular edema caused by RVO in short-term, but long-term effects is needed further observed.

  1. Longstanding refractory pseudophakic cystoid macular edema resolved using intravitreal 0.7 mg dexamethasone implants

    DEFF Research Database (Denmark)

    Brynskov, Troels; Laugesen, Caroline Schmidt; Halborg, Jakob;

    2013-01-01

    Refractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition.......Refractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition....

  2. Ocular hypertension after intravitreal triamcinolone with vitrectomy and phacoemulsification

    Directory of Open Access Journals (Sweden)

    Parke III DW

    2012-06-01

    Full Text Available D Wilkin Parke III, Robert A Sisk, Samuel K Houston, Timothy G MurrayDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USAObjective: To evaluate the effect of adjunctive intravitreal triamcinolone (IVTA on intraocular pressure (IOP in the setting of combined vitrectomy with phacoemulsification.Design: Retrospective case series.Participants: One hundred thirty-one consecutive eyes undergoing nonemergent vitrectomy with phacoemulsification and IVTA were reviewed and included in the analysis. All 131 eyes received 4 mg IVTA at the end of surgery.Methods: Pre- and postoperative IOP, use of pressure-lowering medications, and rate of glaucoma surgery were analyzed. Pre-operative risk factors were analyzed.Main outcome measures: IOP, glaucoma medications, or glaucoma surgery.Results: Secondary ocular hypertension (defined as IOP ≥25 mmHg was found in 28 eyes (21%, the majority during postoperative day 1 only. Twelve eyes (9% had an elevated IOP measurement noted at a visit after the first postoperative day. Five (4% had an IOP rise of ≥10 mmHg over baseline at any time after postoperative day 1. Six (5% required glaucoma medications. One eye required a glaucoma drainage implant for diabetic neovascular angle closure glaucoma, and one eye required enucleation for intractable neovascular glaucoma due to radiation retinopathy. Elevated postoperative IOP was statistically associated with higher baseline IOP and presence of preoperative glaucoma.Conclusions: Therapeutic intravitreal triamcinolone with combined vitrectomy and phacoemulsification causes infrequent and usually mild secondary ocular hypertension. Secondary ocular hypertension is associated with preoperative glaucoma and high IOP.Keywords: glaucoma, cataract, inflammation

  3. Intravitreal bevacizumab for persistent macular edema with proliferative diabetic retinopathy.

    Science.gov (United States)

    Gulkilik, Gokhan; Taskapili, Muhittin; Kocabora, Selim; Muftuoglu, Gulipek; Demirci, Goktug

    2010-12-01

    To evaluate the effectiveness of an intravitreal bevacizumab injection on retinal neovascularization and diabetic macular edema (DME) refractory to laser photocoagulation therapy. Thirty-four eyes of 22 patients with proliferative diabetic retinopathy and DME refractory to laser photocoagulation therapy received an intravitreal injection of 1.25 mg/0.05 ml of bevazicumab. Changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), regression of neovascularization over time, and correlation between BCVA and CMT were evaluated. Follow-up visits were at weeks 1, 2 and 4 and months 3 and 6. Mean BCVA was significantly better than baseline only at week 2 (P = 0.036). Mean CMT decreased significantly from baseline at weeks 1, 2, and 4 (P = 0.001). At months 3 and 6, mean CMT increased, albeit insignificantly (P = 0.804 and P = 1.0). The decrease in fluorescein leakage was moderate in all eyes at the end of week 1. At week 2, there was total resolution of fluorescein leakage in 24 (70.5%) eyes and moderate resolution in 10 (29.5%) eyes. At the end of month 3, the fluorescein leakage was fully resolved in 5 (14.7%) eyes, moderately resolved in 24 (70.5%) eyes, and was similar to baseline in 5 (14.7%) eyes. At month 6, the fluorescein leakage was fully resolved in 3 (8.8%) eyes, moderately resolved in 20 (58.8%) eyes, and was similar to baseline in 11 (32.4%) eyes. A moderate but insignificant negative correlation was found between visual acuity and CMT (P > 0.05). Persistence or recurrence of neovascular tissue after panretinal photocoagulation may be attributed to the production of vascular endothelial growth factor by the residual ischemic retina, which also results in persistent or recurrent DME despite macular grid photocoagulation.

  4. The remote effects of intravitreal anti-VEGF therapy.

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    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.

  5. Batch-related sterile endophthalmitis following intravitreal injection of bevacizumab

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    Morteza Entezari

    2014-01-01

    Full Text Available Background: To report a series of patients with sterile endophthalmitis after intravitreal bevacizumab (IVB injection from 2 different batches of bevacizumab. Materials and Methods: Records of 11 eyes with severe inflammation after IVB injections from two different batches (7 eyes from one and 4 from the other on two separate days were evaluated. Fifteen eyes of 15 patients in one day were treated with one batch and 18 eyes of 17 patients were treated another day using another batch injected for different retinal diseases. Each batch was opened on the day of injection. We used commercially available bevacizumab (100 mg/4 ml kept at 4°C. Severe cases with hypopyon were admitted to the ward and underwent anterior chamber and vitreous tap for direct smear and culture. Results: Pain, redness and decreased vision began after 11-17 days. All had anterior chamber and vitreous reactions and 5 had hypopyon. Antibiotics and corticosteroids were initiated immediately, but the antibiotics were discontinued after negative culture results. Visual acuity returned to pre-injection levels in 10 eyes after 1 month and only in one eye pars plana vitrectomy was performed. Mean VA at the time of presentation with inflammation (1.76 ± 0.78 logMAR decreased significantly (P = 0.008 compared to the initial mean corrected VA (1.18 ± 0.55 logMAR; however, final mean corrected VA (1.02 ± 0.48 logMAR improved in comparison with the baseline but not to a significant level (P = 0.159. Conclusions: We report a cluster of sterile endophthalmitis following intravitreal injection of bevacizumab from the same batch of bevacizumab that has a favorable prognosis.

  6. Change in macular thickness in a case of refractory diabetic macular edema with dexamethasone intravitreal implant in comparison to intravitreal bevacizumab: A case report

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    Ashish Sharma

    2012-01-01

    Full Text Available We report on the significant improvement of central macular thickness in a case of clinically significant macular edema after dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA, USA. Patient presented to us with persistent clinically significant macular edema (CSME in both eyes. Right eye received dexamethasone implant and left eye received two intravitreal bevacizumab injections 1.25 mg/0.05 mL (Avastin®; Genentech Inc., South San Francisco, CA, USA with an interval of four weeks. After six weeks of follow-up, dexamethasone implant in the right eye showed normal macular thickness whereas persistent macular edema (ME was found even after second intravitreal bevacizumab injection in the left eye.

  7. Intracerebroventricular administration of nerve growth factor induces gliogenesis in sensory ganglia, dorsal root, and within the dorsal root entry zone.

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    Schlachetzki, Johannes C M; Pizzo, Donald P; Morrissette, Debbi A; Winkler, Jürgen

    2014-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100β revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root.

  8. Intracerebroventricular Administration of Nerve Growth Factor Induces Gliogenesis in Sensory Ganglia, Dorsal Root, and within the Dorsal Root Entry Zone

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    Johannes C. M. Schlachetzki

    2014-01-01

    Full Text Available Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100β revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root.

  9. Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema.

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    Spandau, U H M; Derse, M; Schmitz-Valckenberg, P; Papoulis, C; Jonas, J B

    2005-08-01

    To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema. The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3-12 months). Main outcome measures were visual acuity and intraocular pressure. Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77). In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used.

  10. Acute-Onset Endophthalmitis Caused by Alloiococcus otitidis following a Dexamethasone Intravitreal Implant

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    Tizana Marchino

    2013-03-01

    Full Text Available Purpose: To report the first case of acute endophthalmitis caused by Alloiococcus otitidis after a dexamethasone intravitreal implant. Methods: A 74-year-old female was treated with intravitreal Ozurdex® in her left eye for central retinal vein occlusion (CRVO. Best-corrected visual acuity (BCVA in the eye was 4/20. Intravitreal injection was uneventful. At 48 h after injection, she developed ocular pain and visual acuity had dropped to light perception. Endophthalmitis associated with intravitreal injection was suspected. Results: The patient did not show a favorable clinical response following systemic, intravitreal, and topical fortified antibiotics. We then performed a vitreous biopsy and removed the Ozurdex implant by pars plana vitrectomy. A vitreous culture was positive for A. otitidis. At the 2-month follow up, no inflammation was observed, but due to CRVO and probably aggravated by endophthalmitis, the fundus showed macular fibrosis. The final BCVA was finger counting at 30 cm in her left eye. Conclusions: In cases of an intravitreal implant associated with endophthalmitis, we recommend removal of the device because it may act as a permanent reservoir of organisms if it remains in the vitreous cavity.

  11. Comparison of dexamethasone intravitreal implant and intravitreal triamcinolone acetonide for the treatment of pseudophakic cystoid macular edema in diabetic patients

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    Dang Y

    2014-09-01

    Full Text Available Yalong Dang,1,* Yalin Mu,2,* Lin Li,3,* Yahui Mu,2 Shujing Liu,2 Chun Zhang,4 Yu Zhu,1 Yimin Xu4 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 2Department of Ophthalmology, Yellow River Hospital, Henan University of Science and Technology, Sanmenxia, Henan Province, 3Department of Ophthalmology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, 4Department of Ophthalmology, Peking University Third Hospital, Haidian District, Beijing, People's Republic of China *These authors contributed equally to this work. Background and objective: Our objective was to investigate the efficacy and safety of dexamethasone (DEX implant for the treatment of pseudophakic cystoid macular edema (PCME in diabetic patients. Study design: This was a prospective, non-randomized, interventional case series of 43 participants. Eighteen patients were enrolled in the DEX implant group and 25 were enrolled in an intravitreal triamcinolone acetonide (IVTA group. Main outcome measures: The primary efficacy measurement was the percentage of patients who gained improvements of more than ten letters in best corrected visual acuity (BCVA during 6 months of follow-up. Other efficacy measurements included change in BCVA, change in central macular thickness (CMT, and number of retreatments. The primary safety evaluation was the percentage of patients with intraocular hypertension and variation in intraocular pressure (IOP during 6 months of follow-up. Other adverse events, such as conjunctival hemorrhage, eye pain, secondary infection, endophthalmitis, noninfectious inflammation, retinal detachment, and implant migration, were also recorded during follow-up. Results: At month 1, we observed that the percentage of patients gaining improvement of more than ten letters was similar in both groups (P=0.625. As patients in the IVTA group were retreated several times, this

  12. Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death

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    Kristiansen Mark

    2011-11-01

    Full Text Available Abstract Background Developing sympathetic neurons depend on nerve growth factor (NGF for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far, either by a candidate gene approach or in mRNA differential display experiments. This is partly because it is difficult to obtain large numbers of sympathetic neurons for in vitro studies. Here, we describe for the first time, how advances in gene microarray technology have allowed us to investigate the expression of all known genes in sympathetic neurons cultured in the presence and absence of NGF. Results We have used Affymetrix Exon arrays to study the pattern of expression of all known genes in NGF-deprived sympathetic neurons. We identified 415 up- and 813 down-regulated genes, including most of the genes previously known to be regulated in this system. NGF withdrawal activates the mixed lineage kinase (MLK-c-Jun N-terminal kinase (JNK-c-Jun pathway which is required for NGF deprivation-induced death. By including a mixed lineage kinase (MLK inhibitor, CEP-11004, in our experimental design we identified which of the genes induced after NGF withdrawal are potential targets of the MLK-JNK-c-Jun pathway. A detailed Gene Ontology and functional enrichment analysis also identified genetic pathways that are highly enriched and overrepresented amongst the genes expressed after NGF withdrawal. Five genes not previously studied in sympathetic neurons - trib3, ddit3, txnip, ndrg1 and mxi1 - were validated by real time-PCR. The proteins encoded by these genes also increased in level after NGF withdrawal and this increase was prevented by CEP-11004, suggesting that these genes are potential targets of the MLK-JNK-c-Jun pathway. Conclusions The sympathetic neuron model is one of the best studied models of neuronal apoptosis. Overall, our microarray data gives a comprehensive

  13. Cholinergic Degeneration and Alterations in the TrkA and p75NTR Balance as a Result of Pro-NGF Injection into Aged Rats

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    Ashley M. Fortress

    2011-01-01

    Full Text Available Learning and memory impairments occurring with Alzheimer's disease (AD are associated with degeneration of the basal forebrain cholinergic neurons (BFCNs. BFCNs extend their axons to the hippocampus where they bind nerve growth factor (NGF which is retrogradely transported to the cell body. While NGF is necessary for BFCN survival and function via binding to the high-affinity receptor TrkA, its uncleaved precursor, pro-NGF has been proposed to induce neurodegeneration via binding to the p75NTR and its coreceptor sortilin. Basal forebrain TrkA and NGF are downregulated with aging while pro-NGF is increased. Given these data, the focus of this paper was to determine a mechanism for how pro-NGF accumulation may induce BFCN degeneration. Twenty-four hours after a single injection of pro-NGF into hippocampus, we found increased hippocampal p75NTR levels, decreased hippocampal TrkA levels, and cholinergic degeneration. The data suggest that the increase in p75NTR with AD may be mediated by elevated pro-NGF levels as a result of decreased cleavage, and that pro-NGF may be partially responsible for age-related degenerative changes observed in the basal forebrain. This paper is the first in vivo evidence that pro-NGF can affect BFCNs and may do so by regulating expression of p75NTR neurotrophin receptors.

  14. Two novel clerodane diterpenenes with NGF-potentiating activities from the twigs of Croton yanhuii.

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    Sun, Yihang; Wang, Meicheng; Ren, Quanhui; Li, Shen; Xu, Jing; Ohizumi, Yasushi; Xie, Chunfeng; Jin, Da-Qing; Guo, Yuanqiang

    2014-06-01

    Nerve growth factor (NGF) and analog reagents to promote the neurite outgrowth of nerve cells against the neuron degeneration are expected to be potentially useful for the medical treatment of Alzheimer's disease. In our focus on the discovery of bioactive diterpenes, we investigated the chemical constituents of the plant Croton yanhuii. This investigation led to the isolation and identification of two novel clerodane diterpenes (1 and 2). Their structures were elucidated on the basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and mass (ESIMS and HR-ESIMS) spectroscopic data analyses. Further biological screenings showed that both of the compounds enhanced NGF-mediated neurite outgrowth from PC12 cells.

  15. Chitosan-L-Lactic Acid Scaffold for the Regeneration of Peripheral Nerve and Its NGF Release Properties

    Institute of Scientific and Technical Information of China (English)

    XU Haixing; YAN Yuhua; LI Shipu

    2009-01-01

    Chitosan-L-lactic acid composite scaffold for the regeneration of peripheral nerve is obtained by grafting L-lactic acid onto the amino groups in chitosan with combined vacuum freezer drier.The composite scaffold was characterized by ATR-FTIR and SEM.The scaffold has a better graft efficiency and has a dense inner layer and a loose outer layer with porous structure,and the pore size is about 100μm.The NGF release properties of the scaffold were investigated.The experimental results showed that,at the 1st day,15.2 ng of NGF on average was released from the scaffold.From day 2 to day 10,the release rate obviously slowed down and 1.64 ng of NGF was released on average every day.After 10 days,the release rate was slower and 10.3 ng of NGF was released on average every day.After 60 days,NGF could also maintained a certain concentration.These properties show that the scaffold is a better carrier for NGF which can be more advantageous to the regeneration of the damaged peripheral nerve.As a result,this composite scaffold would be an ideal candidate for the regeneration of damaged peripheral nerve.

  16. NGF causes TrkA to specifically attract microtubules to lipid rafts.

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    Shona Pryor

    Full Text Available Membrane protein sorting is mediated by interactions between proteins and lipids. One mechanism that contributes to sorting involves patches of lipids, termed lipid rafts, which are different from their surroundings in lipid and protein composition. Although the nerve growth factor (NGF receptors, TrkA and p75(NTR collaborate with each other at the plasma membrane to bind NGF, these two receptors are endocytosed separately and activate different cellular responses. We hypothesized that receptor localization in membrane rafts may play a role in endocytic sorting. TrkA and p75(NTR both reside in detergent-resistant membranes (DRMs, yet they responded differently to a variety of conditions. The ganglioside, GM1, caused increased association of NGF, TrkA, and microtubules with DRMs, but a decrease in p75(NTR. When microtubules were induced to polymerize and attach to DRMs by in vitro reactions, TrkA, but not p75(NTR, was bound to microtubules in DRMs and in a detergent-resistant endosomal fraction. NGF enhanced the interaction between TrkA and microtubules in DRMs, yet tyrosine phosphorylated TrkA was entirely absent in DRMs under conditions where activated TrkA was detected in detergent-sensitive membranes and endosomes. These data indicate that TrkA and p75(NTR partition into membrane rafts by different mechanisms, and that the fraction of TrkA that associates with DRMs is internalized but does not directly form signaling endosomes. Rather, by attracting microtubules to lipid rafts, TrkA may mediate other processes such as axon guidance.

  17. Glycation of the high affinity NGF-receptor and RAGE leads to reduced ligand affinity.

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    Bennmann, Dorit; Kannicht, Christoph; Fisseau, Claudine; Jacobs, Kathleen; Navarette-Santos, Alexander; Hofmann, Britt; Horstkorte, Rüdiger

    2015-09-01

    AGEs are posttranslational modifications generated by irreversible non-enzymatic crosslinking reactions between sugars and proteins - a reaction referred to as glycation. Glycation, a feature of ageing, can lead to non-degradable and less functional proteins and enzymes and can additionally induce inflammation and further pathophysiological processes such as neurodegeneration. In this study we investigated the influence of glycation on the high affinity NGF-receptor TrkA and the AGE-receptor RAGE. We quantified the binding affinity of the TrkA-receptor and RAGE to their ligands by surface plasmon resonance (SPR) and compared these to the binding affinity after glycation. At the same time, we established a glycation procedure using SPR. We found that glycation of TrkA reduced the affinity to NGF by a factor of three, which could be shown to lead to a reduction of NGF-dependent neurite outgrowth in PC12 cells. Glycation of RAGE reduced binding affinity of AGEs by 10-fold.

  18. Treatment Efficacy of NGF Nanoparticles Combining Neural Stem Cell Transplantation on Alzheimer's Disease Model Rats.

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    Chen, Yan; Pan, Cuihuan; Xuan, Aiguo; Xu, Liping; Bao, Guoqing; Liu, Feiei; Fang, Jie; Long, Dahong

    2015-11-21

    Alzheimer's disease (AD) is the most common type of dementia. It causes progressive brain disorder involving loss of normal memory and thinking skills. The transplantation of neural stem cells (NSCs) has been reported to improve learning and memory function of AD rats, and protects basal forebrain cholinergic neurons. Nerve growth factor - poly (ethylene glycol) - poly (lactic-co-glycolic acid)-nanoparticles (NGF-PEG-PLGA-NPs) can facilitate the differentiation of NSCs in vitro. This study thus investigated the treatment efficacy of NGF-PEG-PLGA-NPs combining NSC transplantation in AD model rats. AD rats were prepared by injection of 192IgG-saporin into their lateral ventricles. Embryonic rat NSCs were separated, induced by NGF-PEG-PLGA-NPs in vitro, and were transplanted. The Morris water-maze test was used to evaluate learning and memory function, followed by immunohistochemical staining for basal forebrain cholinergic neurons, hippocampal synaptophysin, and acetylcholine esterase (AchE) fibers. Rats in the combined treatment group had significantly improved spatial learning ability compared to AD model animals (pAlzheimer's disease.

  19. Extremely low nerve growth facior (NGF) activity of sea snake (Hydrophiidae) venoms.

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    Mariam, Khafizova; Tu, Anthony T

    2002-12-01

    Sea snake venoms contain less protein than those of land snakes (Toom et al., 1969). Sea snake venoms lack arginine ester hydrolyzing activity, whereas those of Crotalidae and Viperidae have such activity (Tu et al., 1966). Sea snakes live in salty water, and their venoms may be different from those of land snakes. Because of the difficulty in obtaining sea snake venoms, information about sea snake venoms is quite incomplete. NGF is commonly present in the venoms of land snakes such as Elapidae, Viperidae, and Crotalidae (Cohen and Levi-Montalcini, 1956; Lipps, 2002). It is therefore of interest to investigate the presence or absence of NGF in sea snake venoms. In order to investigate the presence or absence of NGF, five sea snake venoms were selected. Lapemis hardwickii (Hardwick's sea snake) and Acalyptophis peronii venom were obtained from the Gulf of Thailand. Hydrophis cyanocinctus (common sea snake) and Enhydrina schistosa (beaked sea snake) venom were obtained from the Strait of Malacca. Laticauda semifasciata (broad band blue sea snake) venom was also examined and the venom was obtained from Gato Island in the Philippines.

  20. NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiation

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    Labhart Paul

    2007-05-01

    Full Text Available Abstract Background p53 is recognized as a critical regulator of the cell cycle and apoptosis. Mounting evidence also suggests a role for p53 in differentiation of cells including neuronal precursors. We studied the transcriptional role of p53 during nerve growth factor-induced differentiation of the PC12 line into neuron-like cells. We hypothesized that p53 contributed to PC12 differentiation through the regulation of gene targets distinct from its known transcriptional targets for apoptosis or DNA repair. Results Using a genome-wide chromatin immunoprecipitation cloning technique, we identified and validated 14 novel p53-regulated genes following NGF treatment. The data show p53 protein was transcriptionally activated and contributed to NGF-mediated neurite outgrowth during differentiation of PC12 cells. Furthermore, we describe stimulus-specific regulation of a subset of these target genes by p53. The most salient differentiation-relevant target genes included wnt7b involved in dendritic extension and the tfcp2l4/grhl3 grainyhead homolog implicated in ectodermal development. Additional targets included brk, sdk2, sesn3, txnl2, dusp5, pon3, lect1, pkcbpb15 and other genes. Conclusion Within the PC12 neuronal context, putative p53-occupied genomic loci spanned the entire Rattus norvegicus genome upon NGF treatment. We conclude that receptor-mediated p53 transcriptional activity is involved in PC12 differentiation and may suggest a contributory role for p53 in neuronal development.

  1. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant.

    Science.gov (United States)

    Chang-Lin, Joan-En; Attar, Mayssa; Acheampong, Andrew A; Robinson, Michael R; Whitcup, Scott M; Kuppermann, Baruch D; Welty, Devin

    2011-01-05

    To determine the pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone (DEX) intravitreal implant (Ozurdex; Allergan, Inc.). Thirty-four male monkeys (Macaca fascicularis) received bilateral 0.7-mg DEX implants. Blood, vitreous humor, and retina samples were collected at predetermined intervals up to 270 days after administration. DEX was quantified by liquid chromatography-tandem mass spectrometry, and cytochrome P450 3A8 (CYP3A8) gene expression was analyzed by real-time reverse transcription-polymerase chain reaction. DEX was detected in the retina and vitreous humor for 6 months, with peak concentrations during the first 2 months. After 6 months, DEX was below the limit of quantitation. The C(max) (T(max)) and AUC for the retina were 1110 ng/g (day 60) and 47,200 ng · d/g, and for the vitreous humor were 213 ng/mL (day 60) and 11,300 ng · d/mL, respectively. The C(max) (T(max)) of DEX in plasma was 1.11 ng/mL (day 60). Compared with the level in the control eyes (no DEX implant), CYP3A8 expression in the retina was upregulated threefold up to 6 months after injection of the implant (0.969 ± 0.0565 vs. 3.07 ± 0.438; P < 0.05 up to 2-month samples). The in vivo release profile of the DEX implant in an animal eye was similar to the pharmacokinetics achieved with pulse administration of corticosteroids (high initial drug concentration, followed by a prolonged period of low concentration). These results are consistent with those in clinical studies supporting the use of the DEX implant for the extended management of posterior segment diseases.

  2. Panretinal photocoagulation versus intravitreal injection retreatment pain in high-risk proliferative diabetic retinopathy

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    Célia Regina Farias de Araújo Lucena

    2013-02-01

    Full Text Available PURPOSE: To compare pain related to intravitreal injection and panretinal photocoagulation in the management of patients with high-risk proliferative diabetic retinopathy. METHODS: Prospective study including patients with high-risk proliferative diabetic retinopathy and no prior laser treatment randomly assigned to receive panretinal photocoagulation (PRP group or panretinal photocoagulation plus intravitreal ranibizumab (PRPplus group. In all patients, panretinal photocoagulation was administered in two sessions (weeks 0 and 2, and intravitreal ranibizumab was administered at the end of the first laser session in the PRPplus group. Retreatment was performed at weeks 16 and 32 if active new vessels were detected at fluorescein angiography. Patients in the PRPplus group received intravitreal ranibizumab and patients in the PRP group received 500-µm additional spots per quadrant of active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale was used for pain score estimation. The patient was asked about the intensity of pain during the whole procedure (retinal photocoagulation session or intravitreal ranibizumab injection. Statistics for pain score comparison were performed using a non-parametric test (Wilcoxon rank sums. RESULTS: Seventeen patients from PRPplus and 14 from PRP group were evaluated for pain scores. There were no significant differences between both groups regarding gender, glycosylated hemoglobin and disease duration. Mean intravitreal injection pain (±SEM was 4.7 ± 2.1 and was significantly lower (p<0.0001 than mean panretinal photocoagulation pain (60.8 ± 7.8. Twelve out of 17 patients from the PRPplus group referred intensity pain score of zero, while the minimal score found in PRP group was found in one patient with 10.5. CONCLUSION: In patients with high-risk proliferative diabetic retinopathy who needed retreatment for persistent new vessels, there was more comfort for the patient when retreatment

  3. The failure in NGF maturation and its increased degradation as the probable cause for the vulnerability of cholinergic neurons in Alzheimer's disease.

    Science.gov (United States)

    Cuello, A Claudio; Bruno, Martin A

    2007-06-01

    This short review discusses the arguments to consider the dismetabolism of the pathway responsible for both the maturation and degradation of NGF as the culprit of vulnerability of the forebrain cholinergic system to the Alzheimer's disease neuropathology. This summary includes information regarding a novel metabolic cascade converting Pro-NGF to mature NGF in the extracellular space and its ultimate degradation by a metalloprotease. It also describes how this pathway is altered in Alzheimer's disease with the consequential CNS accumulation of proNGF and impairment in the formation of NGF along with increased degradation of this key trophic factor. This metabolic scenario in Alzheimer's disease should result in the failure of NGF trophic support to forebrain cholinergic neurons and thus explaining the vulnerability of these neurons in this neurodegenerative condition.

  4. Intravitreal bevacizumab as an adjunctive therapy before diabetic vitrectomy

    Directory of Open Access Journals (Sweden)

    Ashraf M El-Batarny

    2009-02-01

    Full Text Available Ashraf M El-BatarnyAssistant Professor of Ophthalmology, Tanta University, Egypt; Chief of Vitreoretinal Service, Magrabi Eye and Ear Hospital, Muscat, Sultanate of OmanPurpose: To evaluate the effect of intravitreal injection of Avastin, bevacizumab (IVA on diabetic vitrectomy and on the postoperative course.Methods: Thirty patients undergoing diabetic vitrectomy were distributed to standard vitrectomy (group 1 or vitrectomy with preoperative IVA (group 2. Bevacizumab was injected 5 to 7 days before surgery. Patients of both groups were matched as much as possible according to surgical indication and preoperative visual acuity. Main outcome measures were the feasibility of surgery and the postoperative complications. Feasibility of surgery was evaluated through recording surgical time, intraoperative bleeding, use of endodiathermy, relaxing retinotomies, use of perfluorocarbon liquid (PFCL and silicone oil tamponade.Results: Follow up ranged between 7 and 18 months. There was significant reduction of mean surgical time, bleeding frequency, and diathermy use in group 2 compared to group 1. The rate of PFCL use and relaxing retinotomies were less in group 2 in comparison to group 1. Gas or air was used in 80% of patients in group 2 while silicone oil represented 60% of group 1. Postoperative visual acuity improvement was highly significant in both groups but the difference in both groups was not statistically significant. Vision improved in 87% in group 2 and 80% in group 1. Primary anatomical attachment was achieved in 90.3% in group 2 and 86.6% in group 1. Rate of subsequent surgeries and persistent cataract were higher in group 1. Postoperative bleeding was reported in 26.6% of cases in group 1 and none in group 2. In group 2, no complications related to avastin injection or progression of traction were reported during the preoperative period.Conclusion: Preoperative IVA was helpful in achieving the surgical and anatomical goals by reducing

  5. [Surgery in posterior luxated lens fragments through intravitreal phacofragmentation].

    Science.gov (United States)

    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To assess the intra and postoperative difficulties, the anatomical and functional results after intravitreal phacoemulsification during pars plana vitrectomy for retained intraocular lens fragments. Retrospective, non-comparative case series of 48 eyes who underwent vitrectomy for posterior dislocated lens fragments during phacoemulsification between January 2000 and January 2010. In 11 cases the vitrectomy was performed immediately, within 24 hours, and in 37 cases it was delayed 2 to 10 days after cataract surgery. During pars plana vitrectomy the lens fragments were separated of vitreous strings and then phacoemulsification was performed into the center of vitreous cavity. All cases were performed under local anesthesia by the same surgeon. During vitrectomy PFCL was used in 5 cases to protect central retina. Cases were followed-up at least 6 months. Statistical analysis was performed using Wilcoxon and chi square tests. Mean age in the study group was 65.38% 9.49 years (ranging 52-82 years). The mean visual acuity improved from 0.12% 0.07 (0.04-0.3) preoperatively to 0.3% 0.2 (0.05-0.6) postoperatively (p < 0.01). Mean intraocular pressure decreased postoperatively from 26.24% 9.3 mmHg (16-48 mmHg) to 15.95% 3.69 mmHg(12-24 mmHg) (p < 0.01). In all cases corneal edema and intraocular inflammation ceased after vitrectomy. In those 11 cases operated immediately the intravitreal phacoemulsification time was longer, as well as greater number of intraoperative complication (corneal edema, corneal leakage). In 4 out of these 11 cases (36.36%) severe postoperative retinal complications were noticed (2 cases of retinal detachment, 1 case of choroidal detachment and 1 case of choroidal hematoma). In the delayed group the only postoperative complication was cystoid macular edema in 9 out of 37 cases (24.32%). Removal of retained intraocular lens fragments suspended the intraocular inflammation and normalized intraocular pressure in all cases. Our results are in favor of

  6. Stimulation of cannabinoid CB1 receptors prevents nerve-mediated airway hyperreactivity in NGF-induced inflammation in mouse airways.

    Science.gov (United States)

    Bozkurt, Turgut Emrah; Larsson, Olivia; Adner, Mikael

    2016-04-05

    Cannabinoids are known to inhibit neuronal activity and have significant immunomodulatory effects which suggest a role in inflammatory airway diseases. In the present study, we tested the hypothesis that cannabinoids have both acute and chronic modulatory effects on nerve-mediated contractions in NGF-induced airway inflammation. Contractions induced by electrical field stimulation (EFS) were examined in tracheal segments isolated from male BALB/c mice. Tissues were both used fresh or after four days of culture with NGF to induce airway inflammation, and further exposed to cannabinoid receptor agonists. In order to evaluate nerve density, tracheal segments were also examined by immunohistochemistry after in vitro treatments. The CB1 receptor agonists ACEA and ACPA inhibited the constant train EFS-induced contractions in both fresh and NGF-exposed tracheas, an effect that could be blocked by the CB1 receptor antagonist AM251. Culturing the tissues with NGF up-regulated the frequency-dependent EFS-contractions in isolated tracheas. This up-regulation could be inhibited by concomitant treatment with ACEA or ACPA. The treatment with NGF and/or ACEA did not affect the potency or the maximum response to carbachol. In histological sections, it was recognized that the enhanced effect induced by NGF was associated with an increase in nerve density, which, similarly, could be prevented by ACEA treatment. This study shows that stimulation of cannabinoid CB1 receptors modifies the increase of neuronal activity and density in NGF-induced airway inflammation and directly inhibits cholinergic contractions in the airways by a presynaptic mechanism. These findings indicate a protective role of CB1 receptors in airway inflammation.

  7. Nerve growth factor (NGF)-conjugated electrospun nanostructures with topographical cues for neuronal differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Cho, Young Il; Choi, Ji Suk; Jeong, Seo Young; Yoo, Hyuk Sang

    2010-12-01

    Mesenchymal stem cells (MSCs) were cultivated on the surface of nerve growth factor (NGF)-conjugated aligned nanofibrous meshes for neuronal differentiation. Amine-terminated poly(ethylene glycol) was conjugated to poly(ε-caprolactone) to prepare amine-functionalized block copolymers. The synthesized polymer was electrospun in a rotating drum to prepare aligned nanofibrous meshes. A nerve growth factor was chemically immobilized on the surface-exposed amine groups of the electrospun nanofibrous meshes in the aqueous phase. In vitro release profiles of the nerve growth factor were investigated for NGF-immobilized nanofibrous meshes. The conjugated nerve growth factor was not released for 7 days, while the growth factor physically adsorbed on the nanofibrous meshes showed an initial burst release. MSCs were cultivated on the NGF-conjugated nanofibrous meshes for 5 days, and total RNA was extracted from the cultivated cells. mRNA was extracted from cells for measuring expression levels of neuronal differentiation markers, including nestin, tubulin βIII and map2, in the cultivated stem cells. The conjugation of NGF significantly increased the expression levels of the marker proteins for neuron cells while physically adsorbed NGFs on nanofibrous meshes showed low expression of these marker genes. Furthermore, alignments of nanofibrous meshes clearly increased the expression levels of neuronal makers while the nanofibrous mesh without the topographical cue did not affect neuronal differentiation of the cultivated stem cells. Confocal microscopy revealed that the stem cells on the NGF-conjugated aligned nanofibrous meshes showed intense staining with antibodies against neuronal makers as well as elongated morphology compared to other groups. Thus, the NGF-conjugated nanofibrous meshes with topographical cues significantly increased the neuronal differentiation of mesenchymal stem cells in comparison to NGF-adsorbed nanofibrous meshes.

  8. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease?

    Science.gov (United States)

    Chaldakov, George N; Fiore, Marco; Stankulov, Ivan S; Manni, Luigi; Hristova, Mariyana G; Antonelli, Alessia; Ghenev, Peter I; Aloe, Luigi

    2004-01-01

    The development of atherosclerotic cardiovascular disease is a common comorbidity in patients with the metabolic syndrome, a concurrence of cardiovascular risk factors in one individual. While multiple growth factors and adipokines are identified in atherosclerotic lesions, as well as neurotrophins implicated in both cardiac ischemia and lipid and glucose metabolism, the potential role of neurotrophins in human coronary atherosclerosis and in the metabolic syndrome still remains to be elucidated. Here we describe and discuss our results that represent a novel attempt to study the cardiovascular and metabolic biology of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and mast cells (MC). The local amount of NGF, the immunolocalization of p75 neurotrophin receptor (p75NTR) and the number of MC were correlatively examined in coronary vascular wall and in the surrounding subepicardial adipose tissue, obtained from autopsy cases in humans with advanced coronary atherosclerosis. We also analyzed the plasma levels of NGF, BDNF and leptin and the number of MC in biopsies from abdominal subcutaneous adipose tissue in patients with a severe form of the metabolic syndrome. The results demonstrate that NGF levels are decreased in atherosclerotic coronary vascular tissue but increased in the subepicardial adipose tissue, whereas both tissues express a greater number of MC and a stronger p75NTR immunoreactivity, compared to controls. Metabolic syndrome patients display a significant hyponeurotrophinemia and an increased number of adipose MC; the later correlates with elevated plasma leptin levels. In effect, we provide the first evidence for (i) an altered presence of NGF, p75NTR and MC in both coronary vascular and subepicardial adipose tissue in human coronary atherosclerosis, and (ii) a significant decrease in plasma NGF and BDNF levels and an elevated amount of plasma leptin and adipose MC in metabolic syndrome patients. Together our findings suggest that

  9. Combination of Intravitreal Ranibizumab and Laser Photocoagulation for Aggressive Posterior Retinopathy of Prematurity

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    Ágata Mota

    2012-04-01

    Full Text Available Purpose: To report on 2 cases of aggressive posterior retinopathy of prematurity (ROP treated with intravitreal ranibizumab (Lucentis® and laser photocoagulation. Methods: Two premature females, born at 25 and 26 weeks’ gestation with a birth weight of 530 and 550 g, respectively, with aggressive posterior ROP received combined treatment with laser photocoagulation and intravitreal ranibizumab (0.3 mg [30 µl] to each eye. Structural outcomes were evaluated by indirect ophthalmoscopy and documented by retinography. Results: An intravitreal injection was made at 34 weeks of postmenstrual age in the first case, followed by laser photocoagulation 1 week later. There was a partial regression of ROP with treatment. Five weeks later, neovascularization regrowth with bleeding in both eyes (intraretinal and subhyaloid occurred and retreatment with combined therapy was performed. In the second case, single therapy with laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the confluent photocoagulation in the avascular area, progression to 4A ROP stage occurred 1 week later. Both eyes were retreated 1 week later with intravitreal ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in both cases. There were no signs of systemic or ocular adverse side effects. Conclusion: The cases presented show that combination therapy of indirect laser photocoagulation and intravitreal ranibizumab can be effective in the management of aggressive posterior ROP. Further investigation on anti-VEGF safety in premature infants is necessary . Additional studies are needed to define the role of anti-VEGF in ROP treatment.

  10. Fusarium Endophthalmitis following Cataract Surgery: Successful Treatment with Intravitreal and Systemic Voriconazole

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    Paulo A. Alves da Costa Pertuiset

    2016-01-01

    Full Text Available Purpose. To report a case of postoperative endophthalmitis caused by Fusarium species successfully treated with intravitreal and systemic voriconazole after treatment failure with amphotericin B. Methods. Clinical case report of a 60-year-old immunocompetent woman who presents with endophthalmitis of unknown origin 4 weeks after uneventful cataract extraction and IOL implantation surgery. IOL explantation, vitrectomy with capsular bag removal, vitreous aspiration for culture, and intravitreal injection of amphotericin B (5 μg/0.1 mL were performed. Diagnosis was established by culturing the vitreous aspirate on a Sabouraud agar medium and staining with lactophenol blue solution. Five days later, there was no clinical response. The decision was made to administer a single dose of intravitreal voriconazole (2.5 μg/0.1 mL and oral voriconazole (200 mg BID for 30 days. Results. Fusarium sp. grew on culture. Treatment with local and systemic voriconazole was started after no improvement with vitrectomy, IOL explantation, and intravitreal amphotericin B. After 1 month of treatment, the infection resolved and best-corrected visual acuity was 20/25. Conclusion. In patients with endophthalmitis caused by Fusarium sp., topical and systemic voriconazole treatment should be considered in cases resistant to intravitreal amphotericin B.

  11. Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP).

    Science.gov (United States)

    Konstantinidis, Lazaros; Mameletzi, Evangelia; Mantel, Irmela; Pournaras, Jean-Antoine; Zografos, Leonidas; Ambresin, Aude

    2009-09-01

    Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.

  12. Clinical therapeutic effects of intravitreal Ranibizumab injection combined laser photocoagulation for macular edema in BRVO

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    Bin Liu

    2014-11-01

    Full Text Available AIM: To evaluate the clinical therapeutic efficacy of intravitreal ranibizumab injection combined grid laser photocoagulation for macular edema secondary to branch retinal vein occlusion(BRVO. METHODS: Forty-two confirmed cases(42 eyeswith macular edema secondary to BRVO were randomized into 3 groups, each group contained 14 eyes. The ranibizumab group was received intravitreal injection of ranibizumab(0.05mL, the laser group was received grid laser photocoagulation, and the combined group was received a second therapy of grid laser photocoagulation after 1wk of the intravitreal injection of ranibizumab. Recorded the best-corrected visual acuity(BCVAand the central macular thickness(CMTpreoperative and at 1, 3, 6mo after therapy. RESULTS: The BCVA and the CMT had no differences among three groups pretherapy(P>0.05. While BCVA was much better and CMT was reduced significantly posttherapy than pretherapy in all three groups(PPP>0.05. While the BCVA was better and the CMT was thinner in the combined group than ranibizumab group and laser group at every time point(PPCONCLUSION: The intravitreal ranibizumab injection combined grid laser photocoagulation is an effective treatment method for the macular edema secondary to BRVO, it is more effective in improving BCVA than intravitreal ranibizumab or grid laser photocoagulation alone.

  13. Comparison between intravitreal Ranibizumab and Tramicinolone acetonide for macular edema secondary to central retinal vein occlusion

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    Miao Zeng

    2014-08-01

    Full Text Available AIM:To compare the efficacy and safety of intravitreal ranibizumab to those of triamcinolone acetonide(TAinjection for the treatment of macular edema secondary to central retinal vein occlusion(CRVO.METHODS:This retrospective study included 40 eyes of 40 patients with macular edema associated with CRVO. Twenty patients 20 eyes were treated with intravitreal injection of triamcinolone acetonide(1mg, 0.1mL, the other 20 patients 20 eyes accepted intravitreal ranibizumab(0.5mg, 0.05mL. The change of best corrected visual acuity(BCVA, central macular thickness(CMT, and intraocular pressure(IOPbefore treatment and at 1, 2wk, 1, 2,3,6mo post-injection in the two groups were observed. RESULTS:BCVA was improved at 1, 2wk, 1, 2,3,6mo post-injection in the TA group(PPP>0.05. CMT decreased significantly within each group(PP>0.05. In the TA group, the IOP was significantly higher at 2wk and 4wk than before treatment(PP>0.05. However, the IOP at 1mo was significantly higher in the TA group than that in the ranibizumb group(PCONCLUSION:Intravitreal ranibizumab is an effective and safe treatment method for macular edema secondary to CRVO. It can effectively improve BCVA and reduce CMT without ocular and systemic complications compared with intravitreal TA.

  14. Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes

    DEFF Research Database (Denmark)

    Laugesen, Caroline Schmidt; Ostri, Christoffer; Brynskov, Troels

    2017-01-01

    PURPOSE: There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti-VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes. METHODS: A nationwide...... retrospective review of medical records from 2010 to 2013. RESULTS: We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow-up was 323 days (interquartile range 72-1404 days). Baseline mean visual acuity was 0.57 logMAR (95% CI...... 0.13-1.01) before injections. After an average of 4.7 injections (range 1-15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13-0.95) with a mean improvement of 0.03 (p = 0. 45, 95% CI -0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision...

  15. Intravitreal low molecular weight heparin in PVR surgery.

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    Kumar Atul

    2003-01-01

    Full Text Available Purpose: To evaluate the efficacy of low molecular weight heparin (LMWH in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR. Material and Methods: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each. Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. Results: At each follow-up visit, the study group showed a better media clarity, which was statistically significant ( P = 0.0042. The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33% compared to 3 patients in the control group (20%. Conclusion: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

  16. Intravitreal Devices for the Treatment of Vitreous Inflammation

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    John B. Christoforidis

    2012-01-01

    Full Text Available The eye is a well-suited organ for local delivery of therapeutics to treat vitreous inflammation as well as other pathologic conditions that induce visual loss. Several conditions are particularly challenging to treat and often require chronic courses of therapy. The use of implantable intravitreal devices for drug delivery is an emerging field in the treatment of vitreous inflammation as well as other ophthalmologic diseases. There are unique challenges in the design of these devices which include implants, polymers, and micro- and nanoparticles. This paper reviews current and investigational drug delivery systems for treating vitreous inflammation as well as other pathologic conditions that induce visual loss. The use of nonbiodegradable devices such as polyvinyl alcohol-ethylene vinyl acetate polymers and polysulfone capillary fibers, and biodegradable devices such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid, polycaprolactones, and polyanhydrides are reviewed. Clinically used implantable devices for therapeutic agents including ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and dexamethasone are described. Finally, recently developed investigational particulate drug delivery systems in the form of liposomes, microspheres, and nanoparticles are examined.

  17. Comparison of Two Anesthetic Methods for Intravitreal Ozurdex Injection

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    V. Levent Karabaş

    2015-01-01

    Full Text Available Purpose. To determine whether subconjunctival lidocaine injection maintains additional anesthetic effect during intravitreal Ozurdex injection. Methods. 63 patients who were diagnosed as central or branch retinal vein occlusion and planned to receive Ozurdex injection for macular edema were prospectively included in the study. The patients were randomized into one of the two anesthetic groups. The first group received topical proparacaine drop and lidocaine applied pledget. The second group received subconjunctival lidocaine injection in addition to the anesthetics in group 1. Results. Mean pain score was 1.90±2.39 in group 1 and 1.71 ± 2.09 in group 2 (p=0.746. Mean subconjunctival hemorrhage grade was 1.67±0.17 in group 1 and 0.90±0.14 in group 2 (p=0.001. There was no relationship between the amount of subconjunctival hemorrhage and pain score of the patients. Conclusions. There was no difference in pain scores between the two anesthetic methods. The addition of subconjunctival lidocaine injection offered no advantage in pain relief compared to lidocaine-applied pledgets.

  18. Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides.

    Science.gov (United States)

    Girard, Beatrice; Peterson, Abbey; Malley, Susan; Vizzard, Margaret A

    2016-11-01

    The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, continuous fill, conscious cystometry; (2) innervation and neurochemical coding of the suburothelial plexus of the urinary bladder using immunohistochemistry and semi-quantitative image analyses; (3) neuropeptide protein and transcript expression in urinary bladder of postnatal and adult NGF-OE mice using Q-PCR and ELISAs and (4) the effects of intravesical instillation of a neurokinin (NK)-1 receptor antagonist on bladder function in postnatal and adult NGF-OE mice using conscious cystometry. Postnatal NGF-OE mice exhibit age-dependent (R(2)=0.996-0.998; p≤0.01) increases in Sub and CGRP expression in the urothelium and significantly (p≤0.01) increased peptidergic hyperinnervation of the suburothelial nerve plexus. By as early as P7, NGF-OE mice exhibit a vesicovesical reflex in response to intravesical instillation of saline whereas littermate WT mice require perigenital stimulation to elicit a micturition reflex until P13 when vesicovesical reflexes are first observed. Intravesical instillation of a NK-1 receptor antagonist, netupitant (0.1μg/ml), significantly (p≤0.01) increased void volume and the interval between micturition events with no effects on bladder pressure (baseline, threshold, peak) in postnatal NGF-OE mice; effects on WT mice were few. NGF-induced pleiotropic effects on neuropeptide (e.g., Sub P) expression in the urinary bladder contribute to

  19. ProNGF derived from rat sciatic nerves downregulates neurite elongation and axon specification in PC12 cells

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    Anna Sofia Trigos

    2015-09-01

    Full Text Available Several reports have shown that a sciatic nerve conditioned media (CM causes neuronal-like differentiation in PC12 cells. This differentiation is featured by neurite outgrowth, which are exclusively dendrites, without axon or sodium current induction. In previous studies, our group reported that the CM supplemented with a generic inhibitor for tyrosine kinase receptors (k252a enhanced the CM-induced morphological differentiation upregulating neurite outgrowth, axonal formation and sodium current elicitation. Sodium currents were also induced by depletion of endogenous proNGF from the CM (pNGFd-CM. Given that sodium currents, neurite outgrowth and axon specification are important features of neuronal differentiation, in the current manuscript, first we investigated if proNGF was hindering the full PC12 cell neuronal-like differentiation. Second, we studied the effects of exogenous wild type (pNGFwt and mutated (pNGFmut proNGF isoforms over sodium currents and, whether or not their addition to the pNGFd-CM would prevent sodium current elicitation. Third, we investigated if proNGF was exerting its negative regulation through the sortilin receptor, and for this, the proNGF action was blocked with neurotensin (NT, a factor known to compete with proNGF for sortilin. Thereby, here we show that pNGFd-CM enhanced cell differentiation, cell proportion with long neurites, total neurite length, induced axonal formation and sodium current elicitation. Interestingly, treatment of PC12 cells with wild type or mutated proNGF isoforms elicited sodium currents. Supplementing pNGFd-CM with pNGFmut reduced 35% the sodium currents. On the other hand, pNGFd-CM+pNGFwt induced larger sodium currents than pNGFd-CM. Finally, treatments with CM supplemented with NT showed that sortilin was mediating proNGF negative regulation, since its blocking induced similar effects than the pNGFd-CM treatment. Altogether, our results suggest that proNGF within the CM, is one of the

  20. Minimizando erros na administração de drogas intravítreas Minimizing errors in intravitreal drug injection

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    Shu I Yeh

    2003-01-01

    Full Text Available OBJETIVO: Avaliar possíveis erros na administração de drogas intravítreas para o tratamento da endoftalmite e propor técnica que seja reprodutível e acessível. MÉTODOS: Avaliação de técnicas utilizadas e aferição dos volumes retidos nas agulhas utilizando balança analítica. RESULTADOS: A média e o desvio padrão dos volumes retidos nas agulhas de 26, 22 (25 x 0,7 mm e 30 x 0,7 mm e 18 G (gauge foram 0,051±0,006, 0,056±0,005, 0,055±0,004 e 0,075±0,004, respectivamente, para a marca Ryncos® e 0,050±0,003, 0,056±0,002, 0,063±0,002 e 0,084±0,004, respectivamente, para a marca Becton-Dickinson®. Houve diferença estatisticamente significante entre os volumes retidos das duas marcas para as agulhas de 26, 22 (30 x 0,7 mm e 18 G com p = 0,01, p PURPOSE: To assess evaluate the accuracy of intravitreal drug administration in the treatment of endophthalmitis and to suggest a reproducible and accessible technique for this procedure. METHODS: To assess the retained volumes in needles used for the intravitreal injection of antibiotics using an analytical scale. RESULTS: Means and standard deviations of retained volumes in the 26, 22 ( 25 x 0.7 mm and 30 x 0.7 mm and 18 G were respectively 0.051±0.006, 0.056±0.005, 0.055±0.004 and 0.075±0.004 for needles Ryncos® and 0.050±0.003, 0.056±0.002, 0.063±0.002 and 0.084±0.004 for Becton-Dickinson®. There were statistically significant differences in the retained volumes between the two needle brands for 26, 22 (30 x 0.7 mm and 18 G needles with p = 0.01, p < 0.01 and p < 0.01 respectively. No difference was found only for 25 x 0.7 mm 22 G needle with p = 0.83. CONCLUSION: Most needles used for intravitreal injection hold a retained volume in the reserve needle compartment that should be considered during the injection technique, therefore minimizing errors during intravitreal injection of antibiotics.

  1. Comparison of efficiency of intravitreal ceftazidime and intravitreal cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis

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    Nurettin Deniz

    2013-01-01

    Full Text Available In this study, we evaluated the efficiency of cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis. We compared the findings with the standard dose of ceftazidime (1 mg/0.1 ml. Thirty-six New-Zealand White rabbits were divided into 6 equal groups and were treated with different methods (Group 1 = sham, Group 2 = 0.5 mg/0.1 ml cefepime, Group 3 = 1 mg/0.1 ml cefepime, Group 4 = 2 mg/0.1 ml cefepime, Group 5 = 1 mg/0.1 ml ceftazidime, Group 6 = control. The eyes of rabbits in each group were examined clinically on 1 st , 3 rd , and 6 th day of the experiment. At 6 th day, 0.1 ml vitreous humor aspirates were obtained and plated for quantification on the blood agar and the results were expressed as colony-forming unit/ml. Subsequently, the eyeballs were enucleated and the histopathological evaluation was performed. Our findings denoted beneficial effects of cefepime in treatment groups (especially, in Groups 3 and 4. Intravitreal cefepime may be an alternative drug in the treatment of P. aeruginosa endophthalmitis.

  2. Exposure of PC12 cells to NGF/ethanol results in accelerated differentiation and altered gene expression

    Energy Technology Data Exchange (ETDEWEB)

    White, K.R.; Wooten, M.W. (Auburn Univ., AL (United States))

    1991-03-11

    The role of alcohols in affecting neuromorphogenesis was investigated in the pheochromocytoma cell line, PC12. The effect of ethanol at physiological concentrations in this system leads to accelerated neurite extension in the presence of suboptimal concentrations of NGF. Accelerated morphological differentiation was dependent upon the side chain length of the alcohol and not inhibited by pyrazole. Ethanol/NGF induced neurite extension can be blocked with 50nM of K252a, but not sphingozine, H7, H89, genistein or okadaic acid. Changes in the expression of 17 NGF-induced and/or neuronal transcripts were examined in relationship to time of NGF/ethanol exposure; dose of NGF/ethanol; and side-chain length of NFG/alcohol. The authors studies indicate that ethanol potentiates the effects of NFG and subsequent neurogenesis through both protein kinase C and cAMP-independent pathways. In addition, these data show that ethanol is capable of altering gene expression in a specific manner.

  3. Effects of postnatal anti-NGF on the development of CGRP-IR neurons in the dorsal root ganglion.

    Science.gov (United States)

    Tonra, J R; Mendell, L M

    1998-03-23

    Experiments were undertaken to examine anatomical correlates of physiological effects of rabbit sera raised against nerve growth factor (anti-NGF) on nociceptive afferents. This antiserum has been shown to deplete the population of A-delta high threshold mechanoreceptors and to reduce neurogenic vasodilatation. Because numerous studies implicate calcitonin gene related peptide (CGRP)-containing sensory neurons in these effects, immunocytochemical and anatomical techniques were used to examine the normal development of CGRP-immunoreactive (-IR) neurons in the dorsal root ganglion (DRG) of rats from 13 days to 19 weeks of age, and to compare this to the development in rats treated neonatally (postnatal days 2-14) with anti-NGF. In controls the rate of increase in the mean diameter of CGRP-IR cells was substantially greater between 13 days and 5 weeks of age than it was between 5 weeks and 19 weeks, in contrast to CGRP-negative neurons whose rate of growth remained relatively constant. Anti-NGF had no significant effect on growth rate, but rats treated with anti-NGF exhibited a reduced proportion of CGRP-IR neurons at 5 weeks. This deficit was reversed by 19 weeks unlike the physiological changes. These results indicate independent regulation of CGRP expression and nociceptor physiology by NGF.

  4. The induction of tuftelin expression in PC12 cell line during hypoxia and NGF-induced differentiation.

    Science.gov (United States)

    Leiser, Yoav; Silverstein, Nechama; Blumenfeld, Anat; Shilo, Dekel; Haze, Amir; Rosenfeld, Eli; Shay, Boaz; Tabakman, Rinat; Lecht, Shimon; Lazarovici, Philip; Deutsch, Dan

    2011-01-01

    The tuftelin protein isoforms undergo post-translation modifications, and are ubiquitously expressed in various tissues in embryos, adults, and tumors. Developmental and pathological studies suggested an apparent correlation between oxygen deprivation and tuftelin expression. The aim of the study was therefore to investigate the effect of a pathological insult (hypoxia) and a physiological growth factor (NGF), which antagonistically regulate HIF1 expression, on tuftelin expression using the neuronal PC12 cell model. In the present study, we first demonstrated the expression of tuftelin in PC12 cells, providing an experimental system to investigate the pathophysiological role of tuftelin. Furthermore, we demonstrated the induction of tuftelin during hypoxia by oxygen deprivation and during chemical hypoxia by cobalt chloride. Down-regulation of HIF1α mRNA blocked hypoxia-induced HIF1α expression, and reduced by 89% hypoxia-induced tuftelin expression. In mice, intraperitoneal injection of cobalt chloride significantly induced tuftelin mRNA and protein expression in the brain. During NGF-mediated PC12 differentiation, tuftelin expression was significantly induced in correlation with neurite outgrowth. This induction was partially blocked by K252a, a selective antagonist of the NGF receptor TrkA, indicating the involvement of the TrkA-signaling pathways in tuftelin induction by NGF. Revealing the physiological role of tuftelin will clarify mechanisms related to the "hypoxic genome," and NGF-induced neurotrophic and angiogenic effects.

  5. [The results of wet AMD treatment by intravitreal injections--preliminary report].

    Science.gov (United States)

    Okruszko, Anna; Borucka, Anna I; Ulińska, Magdalena; Szaflik, Jerzy

    2007-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible, severe loss of vision in the developed countries. One of the modern methods of treatment in neovascular form of AMD are repeated intravitreal injections of ranibizumab (Lucentis). Ranibizumab is a recombinant, humanized, monoclonal antibody that neutralizes all biologically active forms of vascular endothelial growth factor A (VEGF-A). The aim of the study was to analyze the results of intravitreal ranibizumab injections in wet AMD patients. There were 57 patients enrolled in the study. 87% of them avoided any loss of visual acuity and 47.3% gained at least one line at visual acuity chart. Authors conclude that treatment with repeated intravitreal injections of ranibizumab is effective in neovascular form of AMD.

  6. One day wonder: Fast resolution of macular edema following intravitreal ranibizumab in retinal venous occlusions

    Directory of Open Access Journals (Sweden)

    Lalit Verma

    2013-01-01

    Full Text Available Macular edema is a significant cause of vision loss in patients with central retinal vein occlusions and branch retinal vein occlusions. Vascular endothelial growth factor (VEGF appears to be a key factor in the pathogenesis of this disease. Anti-VEGF therapy, such as intravitreal ranibizumab provides an effective treatment against vision-threatening macular edema. We report three patients of retinal vein occlusion with macular edema who demonstrated overnight resolution of macular edema following treatment with intravitreal ranibizumab (0.5 mg. 3D optical coherence tomography (Optovue was used as a tool for comparison of the macular thickness before and after treatment. The significant reductions in the central foveal thickness demonstrated in these patients one night after intravitreal injections could have significant influence on modifying current treatment protocols. Early treatment of macular edema related to retinal venous occlusive disease with anti-VEGF injections could result in faster visual rehabilitation in these patients.

  7. 脊髓腹角神经元共存NGF,BDNF,NT3,NT4和GDNF%The Co-expression of NGF, BDNF, NT3, NT4 and GDNF in Neurons of Ventral Horn of Spinal Cord

    Institute of Scientific and Technical Information of China (English)

    李维平; 王廷华; 徐蔚

    2000-01-01

    NGF,BDNF,NT3,NT4和GDNF抗血清,以免疫组织化学方法观察NGF,BDNF,NT3,NT4及GDNF在成年猫L5脊髓腹角神经元是否共存.结果:L5脊髓腹角神经元均含有上述被检测的5种神经营养因子的免疫反应物,表明腹角神经元共存NGF,BDNF,NT3,NT4及GDNF,提示这5种神经营养因子可能与脊髓腹角神经元的生理过程有关.

  8. Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF, and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system

    Directory of Open Access Journals (Sweden)

    Aloe Luigi

    2003-04-01

    Full Text Available Abstract Previous studies on the effect of repeated electro-acupuncture (EA treatments in rats with steriod-induced polycystic ovaries (PCO, EA has been shown to modulate nerve growth factor (NGF concentration in the ovaries as well as corticotropin releasing factor (CRF in the median eminence (ME. In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1, a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p p p p

  9. [Off-label use of intravitreal bevacizumab for severe retinopathy of prematurity].

    Science.gov (United States)

    Alba, L E; Zaldua, R A; Masini, R A

    2015-02-01

    To examine the quality of evidence and the variability in the off-label use of intravitreal bevacizumab for retinopathy of prematurity (ROP). A wide review of the literature was performed using Pubmed, Medline, and Cochrane database, using the words vascular endothelial growth factor (VEGF), retinopathy of prematurity, treatment and bevacizumab. Case reports, case series, reviews, one sistematic review and one randomized controlled trial were found on the use of intravitreal bevacizumab in severe ROP, as monotherapy or combined with láser and/or vitrectomy. The results shown on the use of intravitreal bevacizumab in ROP stage 3+ in zone I or in aggressive posterior ROP are promising. However, uncertainty remains regarding its maximum tolerable dose in the neonatal group, its ocular and systemic safety profile, or its efficacy and bioactivity in a developing child. This report found no significant differences in the recurrence rates of ROP stage 3+ in zone II in patients treated with intravitreal bevacizumab monotherapy in comparison to láser, although the latter is the best option due to long-term safety and efficacy. The use of intravitreal bevacizumab is not indicated in stages 1 and 2 of ROP as the risk of severe visual loss is low and VEFG is necessary for normal retinal vessel development. On the other hand, the use of intravitreal bevacizumab would be contraindicated in stages 4 and 5 because the retinal detachment is accelerated. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature.

    Science.gov (United States)

    Polizzi, Silvio; Mahajan, Vinit B

    2015-12-01

    The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia," "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse events," and "maternofetal complications" in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients.

  11. Cell-type-specific expression and regulation of a c-fos-NGF fusion gene in neurons and astrocytes of transgenic mice.

    Science.gov (United States)

    Onténiente, B; Horellou, P; Neveu, I; Makeh, I; Suzuki, F; Bourdet, C; Grimber, G; Colin, P; Brachet, P; Mallet, J

    1994-02-01

    A mouse line transgenic for nerve growth factor (NGF) was developed using the mouse prepro-NGF cDNA inserted within a plasmid containing the proximal region (-10 to -550 bp) of the c-fos promoter and the transcription termination and polyadenylation signals of the rabbit beta-globin gene. No significant modification of gross behavior or central nervous system anatomy was detected in adult animals as assessed by immunohistochemistry and in situ hybridization for NGF and choline acetyltransferase. The expression of the transgene and the possible regulation of its expression by agents acting on the promoter were investigated in vitro. Despite the presence of an additional pool of NGF mRNA specific to the transgene, basal levels of NGF in the supernatant of transgenic astrocytes were similar to normal ones. On the other hand, transgenic neurons spontaneously synthesized and released levels of NGF two to three times higher than normal neurons, while mRNA levels were barely detectable by conventional Northern blotting. The tissue-specificity of NGF expression was respected, with higher levels in hippocampal than neocortical neurons. Increases of NGF mRNA by agents acting on the promoter could be observed in normal and transgenic astrocytes only after inhibition of the protein synthesis by cycloheximide, suggesting a similar rapid turnover of normal and transgenic transcripts. Cyclic AMP agonists specifically increased the secretion of NGF protein by transgenic astrocytes and neurons, while activators of the protein kinase C had a similar effect on transgenic and normal cells. Differences between amounts of NGF secreted by neurons and astrocytes with regards to their respective content in mRNA suggest that transgenic transcripts are subject to normal cell- and tissue-specific post-transcriptional regulations. Agents acting on the c-fos promoter through the protein kinase C or cyclic AMP routes differentially increased the secretion of NGF by transgenic astrocytes or

  12. Nitration and Glycation Turn Mature NGF into a Toxic Factor for Motor Neurons: A Role for p75(NTR) and RAGE Signaling in ALS.

    Science.gov (United States)

    Kim, Mi Jin; Vargas, Marcelo R; Harlan, Benjamin A; Killoy, Kelby M; Ball, Lauren E; Comte-Walters, Susana; Gooz, Monika; Yamamoto, Yasuhiko; Beckman, Joseph S; Barbeito, Luis; Pehar, Mariana

    2017-06-26

    Glycating stress can occur together with oxidative stress during neurodegeneration and contribute to the pathogenic mechanism. Nerve growth factor (NGF) accumulates in several neurodegenerative diseases. Besides promoting survival, NGF can paradoxically induce cell death by signaling through the p75 neurotrophin receptor (p75(NTR)). The ability of NGF to induce cell death is increased by nitration of its tyrosine residues under conditions associated with increased peroxynitrite formation. Here we investigated whether glycation also changes the ability of NGF to induce cell death and assessed the ability of post-translational modified NGF to signal through the receptor for advanced glycation end products (RAGEs). We also explored the potential role of RAGE-p75(NTR) interaction in the motor neuron death occurring in amyotrophic lateral sclerosis (ALS) models. Glycation promoted NGF oligomerization and ultimately allowed the modified neurotrophin to signal through RAGE and p75(NTR) to induce motor neuron death at low physiological concentrations. A similar mechanism was observed for nitrated NGF. We provide evidence for the interaction of RAGE with p75(NTR) at the cell surface. Moreover, we observed that post-translational modified NGF was present in the spinal cord of an ALS mouse model. In addition, NGF signaling through RAGE and p75(NTR) was involved in astrocyte-mediated motor neuron toxicity, a pathogenic feature of ALS. Oxidative modifications occurring under stress conditions can enhance the ability of mature NGF to induce neuronal death at physiologically relevant concentrations, and RAGE is a new p75(NTR) coreceptor contributing to this pathway. Our results indicate that NGF-RAGE/p75(NTR) signaling may be a therapeutic target in ALS. Antioxid. Redox Signal. 00, 000-000.

  13. The NGF saga: from animal models of psychosocial stress to stress-related psychopathology.

    Science.gov (United States)

    Cirulli, Francesca; Alleva, Enrico

    2009-08-01

    The role of the neurotrophins Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) has been expanding over the last years from trophic factors involved in brain growth and differentiation, to much more complex messengers, involved in psycho-neuro-endocrine adaptations. Much of this research stems from a series of studies inspired by the life-long work of the Nobel laureate Rita Levi-Montalcini. A new field of research started when NGF was found to be released in the bloodstream as a result of psychosocial stressors in male mice. Subsequent studies have shown that, in humans, highly arousing situations also result in increased blood levels of NGF, underlying the unique role of this neurotrophin, compared to other neuroendocrine effectors, and its sensitivity to environmental variables endowed by a social nature. Data are reviewed to support the hypothesis that this neurotrophic factor, together with BDNF, could be involved in the neurobiological changes underlying physiological and pathological reactions to stress that can result in increased vulnerability to disease in humans, including risk for anxiety disorders, or in the complex pathophysiology associated with mood disorders. Indeed, numerous data indicate that neurotrophins are present in brain hypothalamic areas involved in the regulation of hypothalamic-pituitary-adrenal axis, circadian rhythms and metabolism. In addition, there is now evidence that, in addition to the nervous system, neurotrophins exert their effects in various tissue compartments as they are produced by a variety of non-neuronal cell types such as endocrine and immune cells, adipocytes, endothelial cells, keratinocytes, thus being in a position to coordinate brain and body reactions to external challenges. Aim of this review is to discuss the evidence suggesting a role for neurotrophins as multifunctional signaling molecules activated during allostatic responses to stressful events and their involvement in the complex

  14. MicroRNA-221 modulates RSV replication in human bronchial epithelium by targeting NGF expression.

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    Sreekumar Othumpangat

    Full Text Available BACKGROUND: Early-life infection by respiratory syncytial virus (RSV is associated with aberrant expression of the prototypical neurotrophin nerve growth factor (NGF and its cognate receptors in human bronchial epithelium. However, the chain of events leading to this outcome, and its functional implications for the progression of the viral infection, has not been elucidated. This study sought to test the hypothesis that RSV infection modulates neurotrophic pathways in human airways by silencing the expression of specific microRNAs (miRNAs, and that this effect favors viral growth by interfering with programmed death of infected cells. METHODOLOGY: Human bronchial epithelial cells infected with green fluorescent protein-expressing RSV (rgRSV were screened with multiplex qPCR arrays, and miRNAs significantly affected by the virus were analyzed for homology with mRNAs encoding neurotrophic factors or receptors. Mimic sequences of selected miRNAs were transfected into non-infected bronchial cells to confirm the role of each of them in regulating neurotrophins expression at the gene and protein level, and to study their influence on cell cycle and viral replication. PRINCIPAL FINDINGS: RSV caused downregulation of 24 miRNAs and upregulation of 2 (p<0.01. Homology analysis of microarray data revealed that 6 of those miRNAs exhibited a high degree of complementarity to NGF and/or one of its cognate receptors TrKA and p75(NTR. Among the selected miRNAs, miR-221 was significantly downregulated by RSV and its transfection in bronchial epithelial cells maximally inhibited gene and protein expression of NGF and TrKA, increased apoptotic cell death, and reduced viral replication and infectivity. CONCLUSIONS/SIGNIFICANCE: Our data suggest that RSV upregulates the NGF-TrKA axis in human airways by silencing miR-221 expression, and this favors viral replication by interfering with the apoptotic death of infected cells. Consequently, the targeted delivery of

  15. Recycling of intact dense core vesicles in neurites of NGF-treated PC12 cells.

    Science.gov (United States)

    Bauer, Roslyn A; Khera, Rebecca S; Lieber, Janet L; Angleson, Joseph K

    2004-07-30

    Exocytic fusion in neuroendocrine cells does not always result in complete release of the peptide contents from dense core vesicles (DCVs). In this study, we use fluorescence imaging and immunoelectron microscopy to examine the retention, endocytosis and recycling of chromogranin B in DCVs of NGF-treated PC12 cells. Our results indicate that DCVs retained and retrieved an intact core that was available for subsequent exocytic release. The endocytic process was inhibited by cyclosporine A or by substitution of extracellular Ca(2+) with Ba(2+) and the total recycling time was less than 5 min.

  16. Involvement of BDNF and NGF in the mechanism of neuroprotective effect of human recombinant erythropoietin nanoforms.

    Science.gov (United States)

    Solev, I N; Balabanyan, V Yu; Volchek, I A; Elizarova, O S; Litvinova, S A; Garibova, T L; Voronina, T A

    2013-06-01

    Human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles and administered intraperitoneally in a dose of 0.05 mg/kg exhibited a neuroprotective effect in experimental intracerebral posttraumatic hematomas (hemorrhagic stroke) and reduced animal mortality. Human recombinant erythropoietin, native and adsorbed on lactic and glycolic acid copolymer-based nanoparticles, exhibited no antistroke effect on this model. Analysis of reverse transcription PCR products showed that human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles more than 2-fold increased the expression of BDNF and NGF neurotrophins in the rat brain frontal cortex and hippocampus.

  17. Combination of intravitreal bevacizumab and peripheral photocoagulation: an alternative treatment in eales disease.

    Science.gov (United States)

    Cp, Juarez; Al, Gramajo; Jd, Luna

    2013-01-01

    To report the efficacy of combination therapy (bevacizumab and photocoagulation) in a case of Eales Disease this study has been performed. Bevacizumab (Avastin, 1.25 mg/0.05 ml) was injected intravitreously for the treatment of iris and retinal neovascularization in a 56-year old Hispanic female with photocoagulation treatment to control the recurrence of vitreous haemorrhage. Our results revealed that stabilization of the disease and improvement in visual acuity were achieved without any signs of recurrence. Intravitreal bevacizumab in combination with photocoagulation treatment of ischemic retinal areas may be a good alternative for patients with recurrent vitreous haemorrhage due to Eales disease.

  18. Astrocytes and Microglia-Mediated Immune Response in Maladaptive Plasticity is Differently Modulated by NGF in the Ventral Horn of the Spinal Cord Following Peripheral Nerve Injury.

    Science.gov (United States)

    De Luca, Ciro; Savarese, Leonilde; Colangelo, Anna Maria; Bianco, Maria Rosaria; Cirillo, Giovanni; Alberghina, Lilia; Papa, Michele

    2016-01-01

    Reactive astrocytes and activated microglia are the key players in several pathophysiologic modifications of the central nervous system. We used the spared nerve injury (SNI) of the sciatic nerve to induce glial maladaptive response in the ventral horn of lumbar spinal cord and examine its role in the remodeling of the tripartite synapse plasticity. Imaging the ventral horn revealed that SNI was associated with both an early microglial and astrocytic activation, assessed, respectively, by analysis of Iba1 and GFAP expression. Microglia, in particular, localized peculiarly surrounding the motor neurons somata. Perineuronal astrocytes, which play a key role in maintaining the homeostasis of neuronal circuitry, underwent a substantial phenotypic change following peripheral axotomy, producing reactive gliosis. The gliosis was associated with the reduction of glial aminoacid transporters (GLT1 and GlyT1) and increase of neuronal glutamate transporter EAAC1. Although the expression of GABAergic neuronal marker GAD65/67 showed no change, glutamate increase, as demonstrated by HPLC analysis, shifted the excitatory/inhibitory balance as showed by the net increase of the glutamate/GABA ratio. Moreover, endogenous NGF levels were altered in SNI animals and not restored by the intrathecal NGF administration. This treatment reverted phenotypic changes associated with reactive astrocytosis, but failed to modify microglia activation. These findings on one hand confirm the correlation between gliopathy and maladaptive plasticity of the spinal synaptic circuitry, on the other hand add new data concerning the complex peculiar behavior of different glial cells in neuronal degenerative processes, defining a special role of microglia in sustaining the inflammatory response.

  19. Improving treatment provision of Wet AMD with intravitreal ranibizumab.

    Science.gov (United States)

    Ghazala, Fadi; Hovan, Marta; Mahmood, Sajjad

    2013-01-01

    Wet age-related macular degeneration (AMD) treatment using intravitreal ranibizumab needs to be started as soon as possible and treatment must be administered based on regular review to achieve the best results. In clinical practice this tight schedule is a challenge and methods of carrying out such timely treatment is the objective of this quality improvement work. A departmental audit was carried out on the service providing treatment for patients with wet AMD in 2009. This audit identified that the appointment system did not meet the ideal standards and subsequently wet AMD patients' visual outcome were poorer than the standard set in trials where the patients were seen and treated at predetermined intervals. In order to enhance the visual benefit of the administered therapy for our patients we thought it necessary to find ways to see and treat patients sooner as well as reduce time intervals between follow-up appointments. The quality improvement was carried out through redesigning the service in the macular treatment centre of Manchester Royal Eye Hospital. Three main strategies were implemented including: changes to the appointment system, expansion of the treatment facility and employment of additional staff. Following changes made, regular re-audits were used to analyse the effectiveness of the new strategies. The changes introduced have brought appointment standards to the level of Royal College of Ophthalmologists' recommendations. Consequently visual outcomes were approaching the standards set by landmark studies. The visual improvement of treated patients seen in the 2011 audit are comparable to other reports outside clinical trials in the UK. In order to enhance the efficacy of ranibizumab for wet AMD it is essential for treatment to be initiated as soon as possible and administered to patients at the recommended time intervals. The actions we have taken were effective in helping develop a service performing to higher standards.

  20. Choroidal thickness after intravitreal ranibizumab injections for choroidal neovascularization

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    Ellabban AA

    2012-05-01

    Full Text Available Abdallah A Ellabban, Akitaka Tsujikawa, Ken Ogino, Sotaro Ooto, Kenji Yamashiro, Akio Oishi, Nagahisa YoshimuraDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, JapanPurpose: To study changes in choroidal thickness with ranibizumab treatment for choroidal neovascularization (CNV.Design: Prospective case series.Methods: This prospective study consisted of 60 CNV-affected eyes of 60 patients treated with intravitreal injections of ranibizumab using an on-demand protocol after an initial loading phase. The eyes studied included 20 with age-related macular degeneration (AMD, 20 with polypoidal choroidal vasculopathy (PCV, and 20 with myopic CNV. In the eyes with AMD and PCV, choroidal thickness at the fovea was measured with optical coherence tomography using enhanced depth imaging. In eyes with myopic CNV, the choroidal thickness was measured using standard optical coherence tomography without the enhanced depth imaging technique.Results: With ranibizumab treatment, central retinal thickness decreased significantly (P < 0.001 and visual acuity improved significantly (P < 0.001. However, central choroidal thickness (167.2 ± 108.3 µm showed no significant change at 1 month after the loading phase (165.2 ± 107.8 µm, P = 0.120 or at final examination (164.8 ± 107.7 µm, P = 0.115. At baseline, central retinal thickness in eyes with AMD was significantly greater that those with PCV (P = 0.005 or high myopia (P = 0.029. However, central choroidal thickness in eyes with myopic CNV was significantly thinner than in eyes with AMD (P < 0.001 or PCV (P < 0.001. In each type of disease, there was no significant change in central choroidal thickness with ranibizumab treatment.Conclusion: The effect of ranibizumab on the choroidal thickness is minimal, if any.Keywords: choroidal thickness, ranibizumab, optical coherence tomography

  1. The NGF Point-Injection for Treatment of the Sound-Perceiving Nerve Deafness and Tinnitus in 68 Cases

    Institute of Scientific and Technical Information of China (English)

    ZHOU Feng; WU Ping; WANG Li; WANG Hai-tao; ZHANG Shao-bin; LIN Yi; ZHONG Hui; CHEN Yan-hua

    2009-01-01

    To observe the therapeutic effects of the point-injection with nerve growth factor (NGF) for the sound-perceiving nerve deafness and tinnitus. Methods: The 140 cases in this series were randomly divided into a treatment group of 68 cases treated by NGF injection at the points of Yifeng (TE 17) and Wangu (GB 12),and a control group of 72 cases orally taking Xibiling (西比灵) and adenosine triphosphate (ATP) and intramuscular injection with VB1 and VB12. Results: The total effective rate was 78.6% in the treatment group and 31.8% in the control group,with significant difference between the two groups (P<0.05). Conclusion: For treating nervous deafness and tinnitus,NGF point-injection may show good therapeutic effects,but inversely proportional to the illness course,age and the extent of hypoacusis.

  2. [Effects of NGF on chromaffin adrenaline-containing cells of adrenal medulla of rabbits transplanted into brains of mice].

    Science.gov (United States)

    Jousselin-Hosaja, M; Derbin, C

    1993-01-01

    The graft of chromaffin adrenaline-containing (A) cells of rabbit adrenal medulla implanted to mouse brain and treated with NGF contains more survived cells 1 month after grafting than adrenal medulla alone. The cells developed either an intermediate (e.g. chromaffin cell and neuron) or a neuron-like phenotypes accompanied with a decrease in an immunoreactivity for PNMT (phenyletanolamine-N-methyltransferase). A gap junctions and attached plaques were found between grafted cells. The grafts received a synaptic input. The NGF influence on the fate of chromaffin A-containing cells is discussed.

  3. Expression of NGF family and their receptors in gastric carcinoma:A cDNA microarray study

    Institute of Scientific and Technical Information of China (English)

    Jian-Jun Du; Ying-Bin Liu; Ze-Guang Han; Ke-Feng Dou; Shu-You Peng; Bing-Zhi Qian; Hua-Sheng Xiao; Feng Liu; Wei-Zhong Wang; Wen-Xian Guan; Zhi-Qing Gao

    2003-01-01

    AIM: To investigate the expression of NGF family and their receptors in gastric carcinoma and normal gastric mucosa,and to elucidate their effects on gastric carcinoma.METHODS: RNA of gastric cancer tissues and normal gastric tissues was respectively isolated and mRNA was purified.Probes of both mRNA reverse transcription product cDNAs labled with α-33P dATP were respectively hybridized with Atlas Array membrane where NGF and their family genes were spotted on. Hybridized signal images were scanned on phosphor screen with ImageQuant 5.1 software after hybridization. Normalized values on spots were analyzed with ArrayVersion 5.0 software. Differential expression of NGF family and their receptors mRNA was confirmed between hybridized Atlas Array membranes of gastric cancer tissues and normal gastric mucosa, then their effects on gastric carcinoma were investigated.RESULTS: Hybridization signal images on Atlas Array membrane appeared in a lower level of nonspecific hybridization. Both of NGF family and their receptors Trk family mRNA were expressed in gastric cancer and normal gastric mucosa. But adversely up-regulated expression in other tissues and organs. NGF, BDGF, NT-3, NT-4/5, NT-6and TrkA, B and C were down-regulated simultaneously in gastric carcinoma in comparison with normal gastric mucosa. Degrees of down-regulation in NGF family were greater than those in their receptors Trk family. Downregulation of NT-3 and BDGF was the most significant,and TrkC down-regulation level was the lowest in receptors Trk family.CONCLUSION: Down-regulated expression of NGF family and their receptors Trk family mRNA in gastric cancer is confirmed. NGF family and their receptors Trk family probably play a unique role in gastric cancer cell apoptosis by a novel Ras or Raf signal transduction pathway. Their synchronous effects are closely associated with occurrence and development of gastric carcinoma induced by reduction of signal transduction of programmed cell death.

  4. Immunolocalization of NGF and its receptors trkA and p75 in the oviducts of golden hamsters during the estrous cycle.

    Science.gov (United States)

    Weng, Qiang; Shi, ZhanQuan; Watanabe, Gen; Taya, Kazuyoshi

    2009-10-01

    To investigate the physiological roles of nerve growth factor (NGF) in the oviduct of golden hamsters during the estrous cycle, the localization of NGF and its receptors, trkA and p75, were determined by immunohistochemistry. Positive staining of NGF, trkA, and p75 was present in epithelial cells and muscle cells of the infundibulum, ampulla, and isthmus in the oviduct. The intensities of the immunohistochemical signals for NGF, trkA, and p75 did not markedly change in any segment of the oviduct during the estrous cycle. These results suggest that NGF may play autocrine/paracrine roles in oviductal transport, fertilization, capacitation of spermatozoa and early embryonic development in the oviduct of golden hamsters.

  5. Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion in a Chinese Population.

    Science.gov (United States)

    Gu, Xiaoya; Yu, Xiaobing; Song, Shuang; Dai, Hong

    2017-01-01

    The aim of this work was to compare the efficacy of intravitreal dexamethasone implant (Ozurdex) and intravitreal ranibizumab (Lucentis) in the treatment of macular edema (ME) caused by retinal vein occlusion (RVO). Thirty-two ME cases treated with Ozurdex and 32 ME cases treated with ranibizumab were enrolled, with 26 central (C)RVO and 6 branch (B)RVO subjects in each group. We compared the results of best-corrected visual acuity (BCVA), central retinal thickness, number of injections, and intraocular pressure (IOP) at 1, 2, 3, and 6 months after injection. BCVA in both groups at each follow-up were significantly increased compared to baseline with no statistical difference between the groups. Ozurdex and ranibizumab successfully reduced CMT at each follow-up. Both CRVO and BRVO patients had significant between-group differences in the mean number of injections. Among the CRVO patients, IOP in the Ozurdex group was significantly increased compared to baseline and the ranibizumab group at 1, 2, and 3 months postinjection. Intravitreal injection of Ozurdex and ranibizumab can effectively control ME secondary to RVO and increase a patient's BCVA. The advantages of Ozurdex are fewer injections and longer efficacy, while the advantages of ranibizumab include fewer side effects. © 2017 S. Karger AG, Basel.

  6. Early change of central macular thickness after intravitreous triamcinolone or bevacizumab in diabetic macular edema or retinal vein occlusion.

    Science.gov (United States)

    Sonoda, Yasushi; Arimura, Noboru; Shimura, Masahiko; Sakamoto, Taiji

    2011-02-01

    To evaluate the immediate changes after intravitreous triamcinolone acetonide or intravitreous bevacizumab in diabetic macular edema (DME). A nonrandomized interventional study. Type 2 diabetic patients were included. Intravitreous triamcinolone acetonide (4 mg) was injected for 22 eyes with DME and IVB (1.25 mg) for 18 eyes with DME. The early time-dependent changes of central macular thickness were evaluated by optical coherence tomography before and from 1 hour to 1 month after intervention. Intravitreous bevacizumab was also tested in patients with retinal vein occlusion as a control of non-DME. Visual acuity was also examined. Compared with the baseline, central macular thickness of eyes with DME decreased significantly 1 hour after intravitreous triamcinolone acetonide (P central macular thickness was observed significantly from 3 hours after IVB in retinal vein occlusion (P retinal vein occlusion than DME after IVB. Visual acuity improved significantly in DME with intravitreous triamcinolone acetonide or IVB at 1 month (P retinal vein occlusion. Although no conclusion can be drawn, immediate decrease in central macular thickness after intravitreous triamcinolone acetonide might indicate the possible involvement of a nongenomic pathway of triamcinolone acetonide action.

  7. NGF Modulates trkANGFR/p75NTR in αSMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP)

    Science.gov (United States)

    Di Zazzo, Antonio; Sgrulletta, Roberto; Cortes, Magdalena; Normando, Eduardo Maria; Lambiase, Alessandro; Bonini, Stefano

    2015-01-01

    Objective In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. Materials and Methods Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. Results OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both αSMA/p75NTR expression and TGFβ1/IL4 release. These effects were not observed in advanced OCP-FBs. Conclusions Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target. PMID:26569118

  8. Pharmacokinetics of intravitreal 5-flurouracil prodrugs in silicone oil. Experimental studies in pigs

    DEFF Research Database (Denmark)

    Laugesen, Caroline S; Steffansen, Bente; Scherfig, Erik

    2005-01-01

    PURPOSE: To examine the in vivo pharmacokinetics of intravitreal 5-Fluorouracil (5-FU) following tamponade with 5-FU prodrug silicone oil formulations. METHOD: Two different alkoxycarbonyl 5-FU prodrugs denoted C12 and C18 were synthesized and formulated as silicone oil suspensions. A total of 26...

  9. Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate

    Institute of Scientific and Technical Information of China (English)

    Pedro Cuevas; Luis Antonio Outeirio; Carlos Azanza; Javier Angulo; Guillermo Gimnez-Gallego

    2015-01-01

    Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.

  10. Intravitreal Ampicillin Sodium for Antibiotic-Resistant Endophthalmitis: Streptococcus uberis First Human Intraocular Infection Report

    Directory of Open Access Journals (Sweden)

    Raul Velez-Montoya

    2010-01-01

    Full Text Available Purpose. To describe the clinical characteristics, diagnosis, and treatment with intravitreal ampicillin sodium of a postoperative endophthalmitis case due to Streptococcus uberis; an environmental pathogen commonly seen in mastitis cases of lactating cows. Methods. Case Report. A 52-year-old, Hispanic diabetic patient who suddenly developed severe pain and severe loss of vision, following vitrectomy. Results. The patient was diagnosed with postoperative endophthalmitis secondary to a highly resistant strain of Streptococcus uberis that did not respond to intravitreal antibiotics. He was treated with an air-fluid interchange, anterior chamber washout, intravitreal ampicillin sodium (5 mg/0.1 mL, and silicon oil tamponade (5000 ck. The eye was anatomically stabilized, though there was no functional recovery. Conclusion. Streptococcus uberis is an uncommon pathogen to the human eye, which has unique features that help the strain in developing resistance to antibiotics. While treatment with intravitreal ampicillin is feasible, there are still concerns about its possible toxicity.

  11. Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate.

    Science.gov (United States)

    Cuevas, Pedro; Outeiriño, Luis Antonio; Azanza, Carlos; Angulo, Javier; Giménez-Gallego, Guillermo

    2015-01-01

    Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.

  12. Changes in retinal oxygen saturation after intravitreal aflibercept in patients with diabetic macular edema

    DEFF Research Database (Denmark)

    Blindbæk, Søren Leer; Peto, Tunde; Grauslund, Jakob

    2017-01-01

    Design of study: Three months prospective interventional study. Purpose: To evaluate changes in retinal arterial and venous oxygen saturation after intravitreal aflibercept in patients with diabetic macular edema (DME). Methods: We included 17 patients with DME, central retinal thickness (CRT) >300...

  13. Retinal tears and rhegmatogenous retinal detachment after intravitreal injections: its prevalence and case reports

    Science.gov (United States)

    Karabag, Revan Yildirim; Parlak, Melih; Cetin, Gölgem; Yaman, Aylin; Osman Saatci, A.

    2015-01-01

    Purpose To report the prevalence of postoperative retinal tear or rhegmatogenous retinal detachment secondary to intravitreal injections. Methods Surgical and medical records of patients who received intravitreal injections at the practice of a single retina specialist from January 2004 to May 2013 and who were followed for at least 6 months were investigated retrospectively. Results During the study period, a total of 3,907 intravitreal injections were performed in 1,049 eyes of 784 patients (416 males [47%]). The mean number of injections per eye was 3.72 ± 3.43 (range, 1–22). The mean age of the participants was 67.03 ± 13.56 (range, 5–94 years). The mean follow-up time was 31.98 ± 22.86 months (range, 6–144 months). Retinal break or rhegmatogenous retinal detachment occurred in 3 injections of 3 eyes, yielding an overall prevalence of 0.077% per injection and 0.29% per eye. Conclusions Retinal tear and rhegmatogenous detachment are rare complications of intravitreal injection. Precautions should be taken especially in patients having predisposing conditions, such as high myopia, or any other vitreoretinal disorders. PMID:27330458

  14. Retinal pigment epithelium tear formation following intravitreal ranibizumab injection in choroidal neovascularization secondary to choroidal osteoma.

    Science.gov (United States)

    Erol, Muhammet K; Coban, Deniz Turgut; Ceran, Basak Bostanci; Bulut, Mehmet

    2014-09-01

    Choroidal osteoma is an extremely rare osseous tumor of the choroid where choroidal neovascularization (CNV) is the major cause of visual loss. We report the case of a 28-year-old female with CNV secondary to choroidal osteoma, who developed RPE tear after intravitreal ranibizumab treatment.

  15. Clinical study on intravitreal injection of cannabinoid HU-211 for optic nerve damage in glaucoma rats

    Directory of Open Access Journals (Sweden)

    Hui-Feng Liu

    2014-09-01

    Full Text Available AIM: To evaluate the protective effects of intravitreal injection of cannabinoid HU-211 for optic nerve in glaucoma rats, providing the experimental evidence in the treatment of glaucoma optic nerve injury.METHODS: Glaucoma rats(18 eyeswere modeled by electric coagulation sclera surface vein and randomized into 3 groups, group A received intravitreal injection of 1mg/0.1mL cannabinoid HU-211 every other day respectively; group B was given intravitreal injection of 0.1mL water every other day, group C was high intraocular pressure(IOPgroup, 6 eyes were randomly selected for blank control group(group D. IOP was observed every day. The rats were sacrificed after treatment 4wk, froze retina section, HE stain. The density fluctuation of retinal ganglion cell(RGCneurons assessment the optic nerve of rat model with chronic high IOP glaucoma were measured.RESULTS: The apoptosis and damage degree of RGC in group B was obviously higher than that in group A, with statistically significant difference(PP >0.05.CONCLUSION: Intravitreal injection of cannabinoid HU-211 shows obvious protective effect on optic nerve in glaucom rat models.

  16. Role of implants in the treatment of diabetic macular edema: focus on the dexamethasone intravitreal implant

    Directory of Open Access Journals (Sweden)

    Cebeci Z

    2015-11-01

    Full Text Available Zafer Cebeci, Nur KirDepartment of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, TurkeyAbstract: Diabetic macular edema (DME is the leading cause of sight-threatening complication in diabetic patients, and several treatment modalities have been developed and evaluated to treat this pathology. Intravitreal agents, such as anti-vascular endothelial growth factors (anti-VEGF or corticosteroids, have become more popular in recent years and are widely used for treating DME. Sustained release drugs appear to be mentioned more often nowadays for extending the period of intravitreal activity, and corticosteroids play a key role in inhibiting the inflammatory process in DME. A potent corticosteroid, dexamethasone (Ozurdex®, in the form of an intravitreal implant, has been approved for various ocular etiologies among which DME is also one. This review evaluates the role of implants in the treatment of DME, mainly focusing on the dexamethasone intravitreal implant.Keywords: diabetes mellitus, diabetic macular edema, vascular endothelial growth factor, dexamethasone, Iluvien, corticosteroid

  17. Intravitreal bevacizumab for macular edema secondary to branch retinal vein occlusion.

    Science.gov (United States)

    Ehlers, Justis P; Decroos, Francis Char; Fekrat, Sharon

    2011-10-01

    To evaluate the effect of intravitreal bevacizumab on the visual and anatomical outcome in eyes with macular edema secondary to branch retinal vein occlusion. A retrospective, consecutive case series identified 53 consecutive patients with a branch retinal vein occlusion treated with intravitreal bevacizumab. Clinical variables were analyzed, including best-corrected visual acuity, angiographic characteristics, central foveal thickness, and complications. Fifty-three eyes were identified with a mean initial best-corrected visual acuity of 20/137 and final best-corrected visual acuity of 20/96 (P = 0.05). The mean final line change was +1.6 lines (95% confidence interval, +0.7 to +2.3; +8 letters [95% confidence interval, +3.5 to 11.5]). At final follow-up, 28% gained ≥ 3 lines, whereas a loss of >3 lines was seen in 6% of eyes. The mean initial central foveal thickness of 425 μm decreased to 289 μm (P retinal vein occlusion showed improved functional outcomes (e.g., final best-corrected visual acuity, mean line change) as compared with those treated with >6 months of symptoms (P retinal vein occlusion in many subjects. Eyes treated with intravitreal bevacizumab showed a significant reduction in central foveal thickness and improvement in visual acuity. Early treatment with intravitreal bevacizumab resulted in a greater improvement in visual acuity compared with delayed treatment.

  18. Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Benoist d’Azy, Cédric; Pereira, Bruno; Naughton, Geraldine; Chiambaretta, Frédéric; Dutheil, Frédéric

    2016-01-01

    Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and “intravitreal injection*”. To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics). We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections). Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections) and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections). Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384–1.682, p = 0.56) for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta-analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics. PMID

  19. Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Cédric Benoist d'Azy

    Full Text Available Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and "intravitreal injection*". To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics. We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections. Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections. Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384-1.682, p = 0.56 for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta-analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics.

  20. Dexamethasone intravitreal implants for diabetic macular edema refractory to ranibizumab monotherapy or combination therapy.

    Science.gov (United States)

    Gutiérrez-Benítez, L; Millan, E; Arias, L; Garcia, P; Cobos, E; Caminal, M

    2015-10-01

    To determine the effectiveness and local safety of dexamethasone intravitreal implants as a treatment in diabetic macular edema (DME) refractory to intravitreal injections of ranibizumab monotherapy or combination therapy. A retrospective study conducted on patients with DME refractory to ranibizumab monotherapy or combined with other treatments treated with dexamethasone intravitreal implants. The parameters analyzed were visual acuity (VA) by ETDRS (Early Treatment Diabetic Retinopathy Study) charts and foveal thickness by spectral-domain optical coherence tomography (SD-OCT) before the treatment, 2 months after treatment, and at the end of the follow-up. A total of 14 eyes of 14 patients were included, with a mean age of 64 years (SD: 9.5; range 41-78) and a mean follow-up of 7.6 months. The mean VA improved from 53 letters to 59 letters at 2 months (P=.03), and 57 at the end of the follow-up period (P=.3). The mean foveal thickness decreased from 502 μ to 304 μ at 2 months (P=.001), and 376 μ at the end of the follow-up period (P=.009). Further treatment with intravitreal dexamethasone was required in 43% of the patients, and 21% had increased intraocular pressure, which was controlled with topical medication. Intravitreal dexamethasone implant is an effective and locally safe treatment for the management of DME refractory to ranibizumab monotherapy or combined with other treatments. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  1. Anterior segment changes following intravitreal bevacizumab injection for treatment of neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Canut MI

    2011-05-01

    Full Text Available MI Canut1, A Alvarez2, J Nadal3, R Abreu4, JA Abreu5, JS Pulido61Glaucoma Section, 2Barraquer Ophthalmology Centre, 3Retina and Vitreous Unit, Macula Section, Institut Universitari Barraquer, Universidad Autonoma de Barcelona, Barcelona, Spain; 4Retina and Vitreous Unit, University Hospital of La Candelaria, Tenerife 5Glaucoma Section, University Hospital of the Canary Islands, Tenerife, Spain; 6Retina and Vitreous Unit, Ophthalmology Department, Mayo Clinic, Rochester, MN, USABackground: The purpose of this study was to describe anterior segment changes in a prospective, interventional, noncomparative case series of patients with neovascular glaucoma secondary to proliferative diabetic retinopathy treated with intravitreal bevacizumab.Methods: Five consecutive patients with neovascular glaucoma and a refractory, symptomatic elevation of intraocular pressure and pronounced anterior segment congestion received intravitreal bevacizumab 1.25 mg/0.05 mL. Follow-up examinations were performed at 4–16 weeks by the same specialists, with testing performed at hour 48, week 1, and months 1, 3, and 6 after intravitreal bevacizumab.Results: We observed a significant difference (P = 0.021 between initial and mean neovascularization at three months in all the quadrants. At three months, median intraocular pressure was 19 ± 5.38 (range 12–26 mmHg. In three of the five cases, diode laser cyclophotocoagulation was required, and in one case a trabeculectomy was performed. One patient showed complete synechial angle closure 48 hours after treatment which required cyclodestructive procedures to normalize intraocular pressure.Conclusion: Intravitreal bevacizumab achieves complete regression of neovascularization in neovascular glaucoma secondary to proliferative diabetic retinopathy, and this regression is stable when associated with treatment of the underlying disease and should be investigated more thoroughly as an adjunct in the management of neovascular

  2. Accelerated ischemic vascular retinopathy after intravitreally injected bevacizumab for central retinal vein occlusion in elderly patients

    Directory of Open Access Journals (Sweden)

    Isola V

    2013-03-01

    Full Text Available Vincenzo Isola,1 Alfredo Pece,1,2 Claudio Massironi,1 Simone Reposi,1 Fabio Dimastrogiovanni11Department of Ophthalmology, Melegnano Hospital, 2Fondazione Retina 3000, Milano, ItalyBackground: Ischemic changes in the retinal circulation are an uncommon but severe adverse vascular reaction to intravitreal bevacizumab (Avastin®, Genentech, San Francisco, CA, USA/Roche, Basel, Switzerland for central retinal vein occlusion (CRVO. In the two cases reported here, ischemic changes in the retina vasculature following intravitreal bevacizumab for CRVO were observed with the aim of describing the clinical and angiographic features of these changes.Methods: Two elderly patients with recent-onset CRVO received one off-label intravitreal injection of bevacizumab 0.05 mL/1.25 mg.Results: In Case 1, the patient's pre-treatment visual acuity was 20/400. At 3 weeks post injection, the patient could count fingers at a distance of 1 ft (30 cm and fluorescein angiography showed reduction in intraretinal hemorrhages and areas of retinal non-perfusion. However, at 6 weeks these were markedly increased compared with those seen in the photograph taken 3 weeks after treatment. In Case 2, the patient's pre-treatment visual acuity was 20/200. At 1 month post injection, vision had decreased to 20/400 and fluorescein angiography showed severe macular ischemia with a remarkable capillary dropout throughout the macula.Conclusion: Ischemic retinal injury may be an uncommon but severe adverse vascular reaction to intravitreal bevacizumab for CRVO. Although progression of retinal ischemia in CRVO could be observed shortly after intravitreal bevacizumab, whether this is a drug- or procedure-related effect or part of the natural history of the condition remains uncertain.Keywords: Avastin, ischemia, macular infarction, intraretinal hemorrhage, retinal non-perfusion

  3. Effects of NGF and TrkA on GAP-43+ nerve regeneration in rat autotransplanted splenic tissue

    Institute of Scientific and Technical Information of China (English)

    JIANG Deng-jin; GUO Guang-jin; WANG Lin; ZHANG Kun; ZHANG Tian-fei; ZUO Yan-fang

    2005-01-01

    Objective:To study the time-course of the regeneration of GAP-43+ nerve, and the effects of NGF and TrkA on this process. Methods: Adult Wistar rats underwent splenectomy and splenic autotransplantation, or sham-operation. On day 7, 14, 30, 60, 90, 120, and 180 after surgery, the density of GAP-43+ nerve fibers in spleen tissues were measured with the immunohistochemistry followed by computer image analysis. The expressions of GAP-43, NGF and TrkA were determined with in situ hybrdization, and their mRNA levels were detected with RT-PCR and image analysis qualification. Results: (1)The GAP-43+ nerve fibers began their regeneration on 30 d after operation and extended from greater omentum into splenic autotransplants. Density of the nerve fibers gradually became greater and almost normal 180 d after operation. (2) In splenic autografts, the mRNA expression of GAP-43, NGF and TrkA appeared on day 30 after the operation, gradually reached the peak on day 90. Conclusion: The renascent GAP-43+ nerve fibers may come from the greater omentum packaging the splenic autografts and NGF and TrkA can promote the nerval regeneration in the autotransplant spleen tissues.

  4. Effects of Estrogen on ER, NGF, and ChAT Expression in Cerebellum of Aging Female Sprague-Dawley Rat

    Institute of Scientific and Technical Information of China (English)

    CHEN Zheng-li; FAN Guang-li; LUO Qi-hui; ZHU Chun-mei; HUANG Yi-dan

    2007-01-01

    This article discusses the effects of estrogen on the expression of estrogen receptor (ER), nerve growth factor (NGF), and choline acetyltransferase (ChAT) in the cerebellum of rats. The model of aging female rat was established to study the expression and distribution of ER, NGF, and ChAT in the cerebellum following 17β-estradiol treatment using the technique of immunohistochemical ultrasensitive SP in sprague-dawley rat. The immunoreactive productions were distributed in stratum Purkinje cell, nucleus dentatus, nucleus interpositus, and nucleus fastigii of cerebellum, and the ER positive production was mainly located in the plasma, cytoplasmic membrane, and neurite, and also existed in nucleus. The general tendency of the expression of ER, NGF, and ChAT positive production in the cerebellum cortex and nuclei of aging rat significantly decreases, while the intensity and quantity of the immunoreactive production ascends predominantly after 17β-estradiol treatment. Simultaneously, the positive neurite of Purkinje cell shows a similar tendency. The abovementioned results suggest that the estrogen upregulates the expression of NGF and ChAT, and plays a vital role in sustaining and protecting the structure and function of cerebellum neurons. Furthermore, the similarity of their changing tendency implies that they were correlated and cooperated during the course in effect of estrogen on cerebellum. It also showed that the action of estrogen in cerebellum could be via genomic and nongenomic mechanism.

  5. Experimental study on regeneration of ascending tract after spinal cord injury with predegenerated peripheral nerve graft and NGF infusion

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective:To explore the effects of predegenerated peripheral nerve graft (PPNG) combined with nerve growth factor (NGF) infusion on ascending sensory tract regeneration after spinal cord injury.Methods: Fifty female SD rats were randomly divided into 5 groups. Group A was treated with PPNG and NGF infusion, group B with PPNG, group C with NGF infusion, group D and group E were blank and normal control, respectively. Horseradish peroxidase-labled (HRP) tracing method was employed to evaluate the regeneration of injured nerves after 8 weeks. The extent of regeneration in and beyond the nerve graft was determined by counting the number of HRP-labeled fibers intersecting imaginary lines perpendicular to the axis of the graft and cord. For the sake of convenience, according to the relation of the PNG and spinal cord, 6 model zones were divided, including caudal of spinal cord, caudal transition zone, caudal zone in graft, rostral zone in graft, rostral transition zone and rostral of spinal cord. Results: On the transverse section of caudal zone in graft, rostral zone in graft, rostral transition zone, the fibers in group A were significantly higher than that in group B and C (P<0.05). Conclusion: PPNG combined with NGF may significantly promote the regeneration of ascending long tract after spinal cord injury. The regenerative fibers can penetrate the 2 graft-host interface scars.

  6. NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

    Directory of Open Access Journals (Sweden)

    Ryan E. Tomlinson

    2016-09-01

    Full Text Available Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.

  7. The role of NGF in pregnancy-induced degeneration and regeneration of sympathetic nerves in the guinea pig uterus.

    Science.gov (United States)

    Brauer, M M; Shockley, K P; Chávez, R; Richeri, A; Cowen, T; Crutcher, K A

    2000-02-14

    In the guinea pig, pregnancy is associated with a generalised depletion of noradrenaline in uterine sympathetic nerves and, in the areas of the uterus surrounding the foetus, by a complete degeneration of sympathetic nerve fibres. These pregnancy-induced changes have been interpreted as a selective effect of placental hormones on the system of short sympathetic fibres arising from the paracervical ganglia. An alternative explanation is that pregnancy affects the neurotrophic capacity of the uterus. We measured NGF-protein levels in the guinea pig uterine horn, tubal end and cervix at early pregnancy, late pregnancy and early postpartum, using a two-site enzyme-linked immunosorbent assay. For comparative purposes the distribution and relative density of noradrenaline-containing sympathetic nerve fibres were assessed histochemically, and tissue levels of noradrenaline were measured biochemically, using high-performance liquid chromatography with electrochemical detection. In all the uterine regions analysed, NGF-protein levels showed a decline at term pregnancy, but in no case was this change statistically significant. After delivery, NGF-protein levels showed a marked increase in the cervix as well as in both the fertile and empty horns. These results suggest that alterations in NGF-protein do not account for the impairment of uterine sympathetic innervation during pregnancy, but may contribute to their recovery after delivery.

  8. MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES

    Science.gov (United States)

    MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES. C. F. Blackman1, D. E. House2*, S. G. Benane3*, A. Ubeda4, M.A. TrilIo4. 1 National Health and Environmental Effects Research Laboratory, EPA,Research Triangle Park, North Caro...

  9. Effect of NGF combined with citicoline + cerebroprotein hydrolysate on neurobehavioral development and serum indexes in neonatal hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Jian-Ning Zhang

    2016-01-01

    Objective:To analyze the effect of NGF combined with citicoline + cerebroprotein hydrolysate on neurobehavioral development and serum indexes in neonatal hypoxic ischemic encephalopathy.Methods: A total of 68 children with neonatal hypoxic ischemic encephalopathy (HIE) were randomly divided into observation group and control group, control group received supportive treatment + NGF combined with citicoline therapy, observation group received supportive treatment + NGF combined with citicoline and cerebroprotein hydrolysate treatment, and then differences in the levels of neurobehavioral development, creatine kinase and brain band, illness-related indexes,etc. were compared between two groups. Results: Serum nerve indexes NSE and S100B levels as well as myocardial enzyme spectrum-related parameters CK, CK-BB and CK-MB levels of observation group after treatment were lower than those of control group (P<0.05); serum MBP, ET-1, NO and CO levels were lower than those of control group, and FN level was higher than that of control group (P<0.05). Conclusions: NGF combined with citicoline + cerebroprotein hydrolysate therapy for children with HIE can reduce brain tissue damage and optimize physical status, and it is of positive clinical significance.

  10. Catalpol up-regulated NGF,BDNF and mRNA gene expression and improved behavior outcome of rats with ischemic stroke%梓醇上调NGF、BDNF及mRNA表达伴随缺血性脑卒中大鼠神经功能恢复

    Institute of Scientific and Technical Information of China (English)

    刘明; 刘洋; 张易; 孙建宁; 唐婧姝; 玄振玉

    2011-01-01

    目的:观察梓醇对缺血性脑卒中大鼠恢复早期神经功能恢复及缺血周围区大脑皮质神经生长因子(NGF)和脑源性神经营养因子(BDNF)表达的影响.方法:建立大鼠大脑中动脉永久性局灶性缺血模型,行为学观察各组大鼠姿势反射、横木行走和抓握力量;HE染色观察大脑皮质神经元的病理改变;免疫组织化学染色和Realtime PCR检测缺大脑皮质NGF、BDNF蛋白及其mRNA基因表达.结果:假手术组无明显神经功能障碍;与模型组比较,梓醇30、60mg/kg给药组能明显改善缺血性脑卒中大鼠姿势反射,增强横木行走的能力和抓握力量(P<0.05,P<0.01);明显增加完整神经细胞的数量(P<0.01);且梓醇30、60mg/kg给药组NGF、BDNF及mRNA的表达比模型组明显上调(P<0.05,P<0.01).结论:梓醇可上调缺血性脑卒中大鼠大脑皮质NGF、BDNF及mRNA基因表达,促进神经元存活、修复再生,加速其神经功能恢复.%Objective: To investigate the effects of catalpol on behavior outcome of rats with ischemia stroke and the expression patterns of NGF, NGF mRNA, BDNF and BDNF mRNA in the cerebral cortex surrounding the ischemic core..Methods: Permanent cerebral ischemia was induced by middle cerebral artery occlusion in rats which were divided into 6 groups:vehicle, catalpol 15, 30, 60 mg/kg, dl-3n-Butyl Phthalide (NBP) 70 mg/kg and sham group. Animals received drug intragastric administration once a day 3-14 day post-ischemia. Sensorimotor function was evaluated with beam-walking and bar-grasping performance at 3, 7, 10 and 14 day post-ischemia, and attitudinal reflexes were assessed at the same time point. Animals were filled at 14 day post-ischemia. HE staining to observe the injury of neuron of sensorimotor region of corter.Brain sections and brain tissue homogenate were prepared for studying the expression of NGF, NGF mRNA, BDNF and BDNF mRNA in the cerebral cortex surrounding the ischemic core using immunohistocbemistry and

  11. Intravitreal anti-vascular endothelial growth factor agents as an adjunct in the management of Coats′ disease in children

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    Kaul Shalini

    2010-01-01

    Full Text Available We describe the role of intravitreal anti-vascular endothelial growth factor (VEGF agents in Coats′ disease in children. In a prospective, interventional, non-randomized case series, three patients (three eyes aged 16, seven and two years were diagnosed to have Coats′ disease. In Case 1 (16 yr/ male with macular edema, previous laser photocoagulation being unsuccessful, intravitreal pegaptanib sodium (Macugen™ was tried. Case 2 (seven yr/ male and Case 3 (two yr/ female were diagnosed to have Stage 4 Coats′ and underwent external needle drainage, laser photocoagulation, SF6 gas injection and intravitreal injection of bevacizumab (Avastin™. Reduction of exudation and attached posterior pole (Cases 2 and 3 was seen at a follow-up of six months and two months respectively. Intravitreal anti-VEGF agents may be successfully used as adjunct treatment in select cases of Coats′ disease in childhood.

  12. The urokinase plasminogen activator receptor (UPAR) is preferentially induced by nerve growth factor in PC12 pheochromocytoma cells and is required for NGF-driven differentiation.

    Science.gov (United States)

    Farias-Eisner, R; Vician, L; Silver, A; Reddy, S; Rabbani, S A; Herschman, H R

    2000-01-01

    Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma cells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiation and to determine the causal nature of specific events in this differentiation process. Although epidermal growth factor (EGF) elicits many of the same early biochemical and molecular changes in PC12 cells observed in response to NGF, EGF does not induce molecular or morphological differentiation of PC12 cells. The identification of genes whose expression is differentially regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotrophin-driven neuronal differentiation. A "second generation" representational difference analysis procedure now identifies the urokinase plasminogen activator receptor (UPAR) as a gene that is much more extensively induced by NGF than by EGF in PC12 cells. Both an antisense oligonucleotide for the UPAR mRNA and an antibody directed against UPAR protein block NGF-induced morphological and biochemical differentiation of PC12 cells; NGF-induced UPAR expression is required for subsequent NGF-driven differentiation.

  13. Gene Expression and Localization of NGF and Its Cognate Receptors NTRK1 and NGFR in the Sex Organs of Male Rabbits.

    Science.gov (United States)

    Maranesi, M; Zerani, M; Leonardi, L; Pistilli, A; Arruda-Alencar, J; Stabile, A M; Rende, M; Castellini, C; Petrucci, L; Parillo, F; Moura, A; Boiti, C

    2015-12-01

    Experiments were devised to characterize the expression of nerve growth factor, beta polypeptide (NGF), and its cognate receptors neurotrophic tyrosine kinase receptor type 1 (NTRK1) and nerve growth factor receptor (NGFR) in rabbit male sex organs, as well as the concentrations of NGF in both seminal and blood plasma of sexually mature male rabbits. Immunoreactivity and gene expression for NGF and cognate receptors were detected in testis, prostate gland and seminal vesicle. The highest levels of NGF and NTRK1 transcripts were found in the prostate, while intermediate expressions were found in the testis. NGFR transcripts were expressed at the same levels in both testis and prostate and were more abundant than in seminal vesicles. The widespread distribution of NGF in all prostate glandular cells, together with its relative high mRNA abundance, confirms that the prostate of rabbits is the main source of this neurotrophin. In conclusion, the present data suggest that the NGF system is involved in the testicular development and spermatogenesis of rabbits and that NGF may act as a potential ovulation-inducing factor being abundantly present in the seminal plasma.

  14. Expression of Nerve Growth Factor (NGF and Its Receptors TrkA and p75 in the Reproductive Organs of Laying Hens

    Directory of Open Access Journals (Sweden)

    PU Shaoxia

    2016-03-01

    Full Text Available Abstract In order to investigate the expression levels of nerve growth factor (NGF and its receptors (TrkA and p75 in prehierarchical follicles and oviducts of hens, five 130-day-old laying hens were examined by immunohistochemistry and RT-PCR analysis. NGF and its receptors were expressed in theca cells and granulosa cells of prehierarchical follicles, and they were also expressed in the epithelial cells of oviducts. The expression of the genes NGF, TrkA and p75 were significantly different in prehierarchical follicles (p<0.05 or p<0.01, and NGF and TrkA gene expression was significantly different in different parts of oviduct (p<0.05 or p<0.01. The expression of NGF and p75 mRNA levels was highest in large white follicle (LWF, as well as the expression of TrkA in small yellow follicle (SYF. In the oviduct, the expression of NGF was the highest in infundibulum, and lowest in isthmus. These results suggest that NGF may play an important role in the regulation of hen reproduction.

  15. Successful Treatment of Retinal Angiomatous Proliferation with Intravitreal Triamcinolone and Ranibizumab Injections in a 67-Year-Old Male

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    Adnaan Haq

    2014-11-01

    Full Text Available A 67-year-old male who presented to the eye casualty department with deterioration in his vision was diagnosed with retinal angiomatous proliferation. After initial deterioration with ranibizumab intravitreal injections, we have demonstrated successful treatment and stabilised vision with ranibizumab and a single intravitreal triamcinolone injection. Stringent follow-up and top-up ranibizumab injections have stabilised his vision and have shown foveal improvement on optical coherence tomography imaging.

  16. Adult Coats’ Disease Successfully Managed with the Dexamethasone Intravitreal Implant (Ozurdex®) Combined with Retinal Photocoagulation

    OpenAIRE

    Sebastián Martínez-Castillo; Roberto Gallego-Pinazo; Rosa Dolz-Marco; Cristina Marín-Lambíes; Manuel Díaz-Llopis

    2012-01-01

    Purpose: To report a case of Coats’ disease managed with the dexamethasone intravitreal implant Ozurdex® (Allergan, Inc., Irvine, Calif., USA) combined with retinal photocoagulation. Methods: A 46-year-old female with 20/200 visual acuity was diagnosed with Coats’ disease with secondary retinal vasoproliferative tumor. An initial approach was performed with an intravitreal injection of the sustained-release dexamethasone implant Ozurdex. After reattachment of the retina, the telangiectatic ve...

  17. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles.

    Science.gov (United States)

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

    2013-11-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals.

  18. Over-expression of hNGF in adult human olfactory bulb neural stem cells promotes cell growth and oligodendrocytic differentiation.

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    Hany E S Marei

    Full Text Available The adult human olfactory bulb neural stem/progenitor cells (OBNC/PC are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases, however effective delivery of NGF into the CNS parenchyma is still challenging due mainly to its limited ability to cross the blood-brain barrier, and intolerable side effects if administered into the brain ventricular system. An effective method to ensure delivery of NGF into the parenchyma of CNS is the genetic modification of NSC to overexpress NGF gene. Overexpression of NGF in adult human OBNSC is expected to alter their proliferation and differentiation nature, and thus might enhance their therapeutic potential. In this study, we genetically modified adult human OBNS/PC to overexpress human NGF (hNGF and green fluorescent protein (GFP genes to provide insight about the effects of hNGF and GFP genes overexpression in adult human OBNS/PC on their in vitro multipotentiality using DNA microarray, immunophenotyping, and Western blot (WB protocols. Our analysis revealed that OBNS/PC-GFP and OBNS/PC-GFP-hNGF differentiation is a multifaceted process involving changes in major biological processes as reflected in alteration of the gene expression levels of crucial markers such as cell cycle and survival markers, stemness markers, and differentiation markers. The differentiation of both cell classes was also associated with modulations of key signaling pathways such MAPK signaling pathway, ErbB signaling pathway, and neuroactive ligand-receptor interaction pathway for OBNS/PC-GFP, and axon guidance, calcium channel, voltage-dependent, gamma subunit 7 for OBNS/PC-GFP-hNGF as revealed by GO and KEGG. Differentiated OBNS/PC-GFP-hNGF displayed extensively branched cytoplasmic processes, a significant faster growth rate and up modulated the expression of oligodendroglia

  19. Expression of Nerve Growth Factor (NGF) and Its Receptors TrkA and p75 in the Reproductive Organs of Laying Hens

    OpenAIRE

    PU Shaoxia; QU Changwei; Li, Zhi; Li, Yansen; Li, Chunmei

    2016-01-01

    Abstract In order to investigate the expression levels of nerve growth factor (NGF) and its receptors (TrkA and p75) in prehierarchical follicles and oviducts of hens, five 130-day-old laying hens were examined by immunohistochemistry and RT-PCR analysis. NGF and its receptors were expressed in theca cells and granulosa cells of prehierarchical follicles, and they were also expressed in the epithelial cells of oviducts. The expression of the genes NGF, TrkA and p75 were significantly differen...

  20. Macular Hole Progression after Intravitreal Bevacizumab for Hemicentral Retinal Vein Occlusion

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    Manish Nagpal

    2011-01-01

    Full Text Available Macular edema secondary to retinal vein occlusion is commonly being treated with off-label intravitreal bevacizumab with good outcomes. A significant reduction in macular edema and improvement in visual acuity is seen following such a treatment with no serious adverse effects. In the reported case, a full-thickness macular hole was noticed one month after intravitreal bevacizumab for macular edema secondary to hemicentral retinal vein occlusion. On a detailed review of the pre- and postoptical coherence tomography scans, it was realized that there was a preexisting stage 2-3 macular hole which was masked by the hemorrhages and edema at the fovea and the macular hole had progressed following the injection.

  1. LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM

    DEFF Research Database (Denmark)

    Freiberg, Florentina J; Brynskov, Troels; Munk, Marion R

    2017-01-01

    PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 2016...... at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were.......0074% per injection (95% CI: 0.0070-0.0078%). Positive cultures were found in 4 out of 10 presumed endophthalmitis cases. CONCLUSION: The standardized sterile technique in an operation room with laminar airflow showed very low rates of endophthalmitis at three European sites....

  2. Combined treatment of exudative age related macular degeneration with photodynamic therapy and intravitreal triamcinolone

    Directory of Open Access Journals (Sweden)

    José Mª Ruiz-Moreno

    2008-03-01

    Full Text Available José Mª Ruiz-Moreno1,2, Javier A Montero21Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain; 2Vitreo-Retinal Unit, Alicante Institute of Ophthalmology, Alicante, SpainAbstract: Choroidal neovascularization (CNV secondary to age related macular degeneration is among the leading causes of legal blindness in developed countries. Photodynamic therapy (PDT with verteporfin induces CNV closure causing little damage to healthy tissue, but the need to re-treat may lead to low final visual acuity at an unacceptable cost. The association of intravitreous triamcinolone or antiangiogenic drugs with PDT has been used in order to reduce these limitations of the therapy. The combination of PDT and intravitreous triamcinolone, its complications and outcome at one and two-year follow-up are discussed.Keywords: age related macular degeneration, choroidal neovascularization, photodynamic therapy, steroid, triamcinolone

  3. Enhanced presence of NGF and mast cells number in nasal cavity after autologous stimulation: relation with sensorineural hearing deficit.

    Science.gov (United States)

    Salvinelli, F; Frari, V; Rocco, M L; Rosso, P; Aloe, L

    2015-01-01

    Nerve growth factor (NGF) is a neurotrophin which promote and regulate the survival of neurons in the peripheral nervous system. We aimed to evaluate the nasal NGF expressions of mast cells in healthy patients after stimulation with sterilized isotonic solution delivered at high pressure. The first part of the study was made with 21 voluntary individuals. The middle third of the inferior turbinate epithelial cells on the right nostril was scraped using a sterile curette and indicated as (pre), than a spray of sterilized isotonic solution at high pressure on the left nostril was delivered and 25 minutes later a similar stimulation was delivered on the same nostril. The stimulation was made with a specific spray. The middle third of the inferior turbinate epithelial cells on the left nostril was scraped using a sterile curette and indicated as (post). Forced nasal stress induced by local delivery of high pressure physiological solution causes an increase in the number of mast cells and enhances level of NGF in the nasal fluid compared to the control subjects. So based on the first part of our study, since NGF is universally known as effective in protection and repairing of neural cells damage, we started the second part and gave a treatment on the same patients, to increase NGF levels with a six months daily therapy and observed the variations in Sensorineural Hearing Loss (SNHL) and tinnitus intensity from the beginning to the end of the therapy. All patients received sterilized isotonic solution at high pressure (pression emission level: PEL): 7 g/sec for 0.5 sec (emission time: ET) in both nostrils. 25 minutes later a similar stimulation was delivered twice a day. The control group (21 pts) received normal therapy with betahistine dihydrochloride 16 mg twice a day. Upon acuphenometry, there was a lower intensity of tinnitus and the improvement was signaled by the patients. Patients with SNHL treated with conventional therapy had a slight worsening, while the

  4. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

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    Villegas VM

    2014-05-01

    Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

  5. Intravitreal ranibizumab for the treatment of choroidal neovascularization secondary to ocular toxoplasmosis

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    Nikunj J Shah

    2011-01-01

    Full Text Available The purpose of the study was to report a case of choroidal neovascularization (CNV secondary to ocular toxoplasmosis in an 18-year-old female patient. She was treated with a single intravitreal injection of ranibizumab. The CNV resolved as confirmed by fluorescein angiography and optical coherence tomography (OCT. The visual acuity improved to 20/30, which was maintained till the last follow-up visit at two years, without requisition of a repeat injection.

  6. Efficacy of intravitreal ranibizumab injection combined with macular grid photocoagulation for diabetic macular edema

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    Hu-Lin Jiang

    2014-07-01

    Full Text Available AIM:To evaluate the clinical efficacy of intravitreal injection of ranibizumab combined with macular grid photocoagulation for diabetic macular edema(DME.METHODS:Totally 60 eyes(60 patientswith DME were randomly divided into 2 groups: 30 eyes of simple injection group underwent intravitreal injection of ranibizumab, and 30 eyes of combined treatment group underwent intravitreal injection of ranibizumab and macular grid photocoagulation 1wk later. The best corrected visual acuity(BCVA, central macular thickness(CMTmeasured by optical coherence tomography(OCTand postoperative complications were observed.RESULTS:In simple injection group, the BCVA after operation were separately 0.390±0.075(4wk, 0.367±0.088(8wkand 0.319±0.064(12wk,the CMT after operation were separately 221.63±112.34μm(4wk, 337.73±99.56μm(8wkand 432.92±100.46μm(12wk, which were much better than pre-operation. But during follow-up, the BCVA presented down trend and the CMT was on the rise slowly. In combined treatment group, the BCVA after operation were separately 0.385±0.036(4wk, 0.382±0.079(8wkand 0.377±0.097(12wk,the CMT after operation were separately 249.77±106.55μm(4wk, 270.40±92.88μm(8wkand 275.84±97.34μm(12wk, which were satisfactory and steady during follow-up, better than simple injection group(PCONCLUSION:Intravitreal injection of ranibizumab can effectively improve visual acuity and decrease central foveal thickness for patients with DME, combining with macular grid photocoagulation can ensure therapeutic effects steady and permanent.

  7. Transformational change: nurses substituting for ophthalmologists for intravitreal injections – a quality-improvement report

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    Michelotti MM

    2014-04-01

    Full Text Available Monica M Michelotti,1 Salwa Abugreen,2 Simon P Kelly,1 Jiten Morarji,1 Debra Myerscough,2 Tina Boddie,2 Ann Haughton,1 Natalie Nixon,2 Brenda Mason,1 Evangelos Sioras11Ophthalmology Department, Royal Bolton Hospital NHS Foundation Trust, Bolton, UK; 2Ophthalmology Department, East Lancashire NHS Trust, Blackburn, UKBackground: The dramatic increase in need for anti-vascular endothelial growth factor (anti-VEGF intravitreal therapy in the treatment of retinal disease and the absence of an equivalent increase in ophthalmologists to undertake such intravitreal injections created a patient-safety risk. Timing of intravitreal therapy (IVT is critical to prevent vision loss and local clinics lacked capacity to treat patients appropriately. We aimed to improve capacity for IVT by nurse injections.Materials and methods: A multidisciplinary prospective service-improvement process was undertaken at two adjacent general hospitals in the northwest of England. IVT injections by nurses were a principal component of solution development. After we had obtained appropriate institutional approval, experienced ophthalmic nurses were trained, supervised, and assessed to undertake IVT. Ophthalmologists directly supervised the first 200 injections, and a retina specialist was always on site.Results: Nurses undertook 3,355 intravitreal injections between June 2012 and November 2013, with minor adverse events (0.3% subconjunctival hemorrhage and corneal abrasion. There were no patient complaints at either hospital.Conclusion: Experienced ophthalmic nurses quickly learned how to perform such injections safely. IVT by nurses was well accepted by patients and staff. Hospital A trained three nurses sequentially for improved flexibility in scheduling. Novel use of appropriately trained nonmedical staff can improve efficiency and access in an overburdened service with time-sensitive disease. Retinal assessment was undertaken by ophthalmologists only. Improved access to IVT

  8. Intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma

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    Zheng-Jun Hu

    2015-05-01

    Full Text Available AIM: To observe the clinical curative effect of intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma(NVG.METHODS:Totally 25 eyes of 25 patients with NVG who underwent intravitreal Bevacizumab injection of 1.0mg(0.05mL, after the regression of iris neovascularization, 5 eyes with anterior chamber paracentesis fluid auxiliary controlled intraocular pressure. After 2wk, patients were treated by trabeculectomy and phacomulsification(9 eyes were implanted intraocular lens. The changes and complications of intraocular pressure, visual acuity, corneas and neovessels were observed after surgery, and followed up 12mo.RESULTS:After injection Bevacizumab in 25 eyes, iris neovascularization of 20 eyes subsided in 3~5d, and 5 eyes subsided in 7d. After controlling intraocular pressure, count of the corneal endothelial cell were 1 629±226mm2, and none suffered decompensation of corneal endothelium after two-surgery of trabeculectomy and phacomulsification. After followed up 12mo, intraocular pressure of 20 eyes were controlled in normal range; 2 eyes could control in normal range after treated by a kind of anti-glaucoma medicine and 3 eyes was 34~38mmHg after treated by anti-glaucoma medicine. 9 eyes had improved vision after implanted intraocular lens.CONCLUSION:Intravitreal Bevacizumab injection can subside iris and anterior chamber angle neovascularization effectively in a short time and reduce intraocular pressure. It can also reduce the risk of bleeding during operation or after operation. Intravitreal Bevacizumab injection combined with two-surgery of trabeculectomy and phacomulsification can treat neovascular glaucoma effectively.

  9. Intravitreal bevacizumab (Avastin treatment of diffuse diabetic macular edema in an Indian population

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    Kumar Atul

    2007-01-01

    Full Text Available Background: To report the anatomic and visual acuity response after intravitreal bevacizumab (Avastin in patients with diffuse diabetic macular edema. Design: Prospective, interventional case series study. Materials and Methods: This study included 20 eyes of metabolically stable diabetes mellitus with diffuse diabetic macular edema with a mean age of 59 years who were treated with two intravitreal injections of bevacizumab 1.25 mg in 0.05 ml six weeks apart. Main outcome measures were 1 early treatment diabetic retinopathy study visual acuity, 2 central macular thickness by optical coherence tomography imaging. Each was evaluated at baseline and follow-up visits. Results: All the eyes had received some form of laser photocoagulation before (not less than six months ago, but all of these patients had persistent diffuse macular edema with no improvement in visual acuity. All the patients received two injections of bevacizumab at an interval of six weeks per eye. No adverse events were observed, including endophthalmitis, inflammation and increased intraocular pressure or thromboembolic events in any patient. The mean baseline acuity was 20/494 (log Mar=1.338±0.455 and the mean acuity at three months following the second intravitreal injection was 20/295 (log Mar=1.094±0.254, a difference that was highly significant ( P =0.008. The mean central macular thickness at baseline was 492 µm which decreased to 369 µm ( P =0.001 at the end of six months. Conclusions: Initial treatment results of patients with diffuse diabetic macular edema not responding to previous photocoagulation did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular thickness and improvement in visual acuity at three months but the effect was somewhat blunted, though still statistically significant at the end of six months.

  10. Cardiovascular involvement in patients with diabetic macular oedema treated with intravitreal ranibizumab in routine clinical practice.

    Science.gov (United States)

    Díaz-Rodríguez, R; Abreu-González, R; Dolz-Marco, R; Gallego-Pinazo, R

    2017-07-01

    To determine the cardiovascular events in naïve patients with diabetic macular oedema, before and after being treated with intravitreal ranibizumab. A retrospective and descriptive study was conducted on patients with diabetic macular oedema and foveal involvement, who started treatment with intravitreal ranibizumab in 2014 in the Hospital Universitario Nuestra Señora de Candelaria and the Hospital Universitario y Politécnico La Fe. During the follow-up until August 2015, a record was made of parameters, including the prevalence and incidence of stroke and myocardial infarction. Among the 1,324 intravitreal ranibizumab injections administered in 2014, only 159 of them corresponded to treatment initiation in 99 patients, with more than half requiring treatment of both eyes. The study patients included 58.4% males, in the 6th decade of life (Mean=65.93±11.24 years), non-smokers (86.7%), type 2 diabetes (91.9%), hypertension (70.7%), and with dyslipidaemia (65.7%). Prior to treatment initiation, it was found that 6 patients (6.1%) suffered from an acute myocardial infarction, and 8 (8.1%) from stroke, and only one (1%) with post-stroke (P=.039). In our experience it seems that the intravitreal ranibizumab in diabetic macular oedema could be a safe alternative in patients with a history of stroke and myocardial infarction. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Combined intravitreal bevacizumab with phacoemulsification in visually significant cataract and visually significant exudative maculopathy

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    Ahmad Mansour

    2011-01-01

    Full Text Available Purpose : We investigated the visual outcome of combined phacoemulsification with intravitreal bevacizumab, in eyes with dense cataract and visually significant exudative maculopathy. Materials and Methods : Prospective longitudinal pilot study of consecutive patients treated by two surgeons in 2006, using intravitreal bevacizumab at the end of phacoemulsification. The historical control group consisted of consecutive subjects with exudative maculopathy and dense cataract treated by the same surgeons with the help of phacoemulsification without intravitreal bevacizumab prior to 2006. Results : Thirty-one treated patients had the mean (SD logMar best corrected visual acuity improving from - 1.48 (0.50 preoperatively to - 0.67 (0.38 in the first postoperative week ( p < 0.001, to - 0.64 (0.40 in the first postoperative month ( p < 0.001, and to - 0.62 (0.42 ( p < 0.001 on the last follow-up (mean 4.2 months, range 1 - 9 months. Fourteen control patients had the mean (SD logMar best corrected visual acuity improving from - 1.78 (0.79 preoperatively, to - 0.91 (0.53 in the first postoperative week ( p < 0.001, to - 0.86 (0.45 in the first postoperative month ( p < 0.001, and to - 0.90 (0.47 ( p < 0.001 on the last follow- up (mean 19.6 months, range 1 - 49 months. Initial visual acuities, final visual acuities, and percentage of visual improvement at one month were all not significantly better in the intervention compared to the control group at one month. In the study group, the fovea was flattened at the one-month follow-up, by 90-diopter slit lamp examination and / or Optical coherence tomography. Conclusion : The combination of intravitreal bevacizumab and phacoemulsification is beneficial for maximal visual rehabilitation in the first postoperative month.

  12. INTRAVITREAL ANTI-VEGF TREATMENT IN EYES WITH COMBINED CHOROIDAL NEOVASCULARISATION AND VITREOMACULAR TRACTION SYNDROME

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    Rotsos, Tryfon; Sagoo, Mandeep; da Cruz, Lyndon; Andrews, Richard; Dowler, Jonathan

    2010-01-01

    Abstract Purpose: To report the effect of intravitreal anti VEGF injections (IVI) on visual acuity (VA) in eyes with choroidal neovascularisation (CNVM) and coexistent vitreomacular traction (VMT) or when VMT has developed during the course of treatment. Methods: Retrospective interventional case series of 7 eyes in 7 patients. VMT was monitored with serial optical coherence tomography scans. Results: The aetiology of the CNVM was wet age-related macular degeneration in 5 e...

  13. Microperimetric changes after intravitreal triamcinolone acetonide injection for macular edema due to central retinal vein occlusion.

    Science.gov (United States)

    Senturk, Fevzi; Ozdemir, Hakan; Karacorlu, Murat; Karacorlu, Serra Arf; Uysal, Omer

    2010-09-01

    The purpose of this study was to evaluate the effect of intravitreal triamcinolone acetonide on macular function in cases of macular edema because of central retinal vein occlusion. Twelve eyes of 12 patients with central retinal vein occlusion were included in this study. In each eye, at baseline and 1, 3, and 6 months after intravitreal triamcinolone acetonide injection, logarithm of the minimum angle of resolution visual acuity, macular sensitivity, fixation stability and fixation location by MP-1 microperimetry, and foveal thickness by optical coherence tomography were assessed. Patients' ages ranged from 50 to 75 years (mean +/- SD, 59 +/- 8 years). All patients were classified as nonischemic. At 1, 3, and 6 months, the mean foveal thickness had decreased from 453 +/- 108 microm to 254 +/- 40.3 microm, 297 +/- 90 microm, and 320 +/- 82 microm and the mean retinal sensitivity had increased from 5.5 +/- 3.3 dB to 9.4 +/- 3.5 dB, 7.8 +/- 3.3 dB, and 7.2 +/- 4.2 dB, respectively. At baseline, fixation was stable in one, relatively unstable in six, and unstable in five eyes. However, 6 months after intravitreal triamcinolone acetonide injection, fixation was stable in 8, relatively unstable in 3, and unstable in one. At baseline, in eyes with macular edema, fixation location was predominantly central in 2, poor central in 4, and predominantly eccentric in 6. And 6 months after treatment, fixation location was predominantly central in 8, poor central in 3, and predominantly eccentric in 1. In eyes with macular edema in central retinal vein occlusion, a short-term improvement in retinal sensitivity and fixation properties can be achieved by intravitreal triamcinolone acetonide injection.

  14. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

    OpenAIRE

    Villegas VM; Gold AS; Berrocal AM; Murray TG

    2014-01-01

    Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 child...

  15. Immunolocalization of nerve growth factor (NGF) and its receptors (TrkA and p75LNGFR) in the reproductive organs of Shiba goats.

    Science.gov (United States)

    Ren, LongQuan; Medan, Mohamed S; Weng, Qiang; Jin, Wanzhu; Li, ChunMei; Watanabe, Gen; Taya, Kazuyoshi

    2005-06-01

    The objective of this study was to determine the immunolocalization of NGF and its receptors (TrkA and p75LNGFR) in the reproductive tract of the Japanese Shiba goats. Five adult goats were used in this study and sections of ovaries, uteri and oviducts were immunostained by the avidin-biotin-peroxidase complex method (ABC). The results showed that NGF and its receptors (TrkA and p75LNGFR) were expressed in granulosa cells, theca cells, interstitial cells and lutein cells in ovaries. Immunoreactions for NGF, TrkA and p75LNGFR were also detectable in epithelial cells and muscle cells of the ampulla and isthmus of the oviduct, and in epithelial cells and uterine glands of the uterus. These results strongly suggest autocrine and paracrine regulation of reproductive function by NGF in the reproductive tract of female Shiba goats.

  16. Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats.

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    Eren Çerman

    Full Text Available Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP labelled bone marrow derived stem cells (BMSC and left eyes with balanced salt solution (Sham. Animals were grouped as Baseline (n = 51, Diabetic (n = 45, Diabetic+BMSC (n = 45 eyes, Diabetic+Sham (n = 45 eyes, Healthy+BMSC (n = 6 eyes, Healthy+Sham (n = 6 eyes. Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function.

  17. Development of a dexamethasone intravitreal implant for the treatment of noninfectious posterior segment uveitis.

    Science.gov (United States)

    Whitcup, Scott M; Robinson, Michael R

    2015-11-01

    Uveitis is a group of ocular inflammatory disorders that can lead to severe vision loss. Despite advances in anti-inflammatory therapy, many patients are resistant to or intolerant of existing treatments. A biodegradable, sustained-release implant, dexamethasone intravitreal implant 0.7 mg (Ozurdex), has been developed to deliver dexamethasone to target tissues in the posterior segment of the eye, minimizing systemic drug exposure and limiting side effects. The implant releases dexamethasone over a period of up to 6 months as the poly(D,L-lactide-co-glycolide) polymer matrix of the implant is metabolized to carbon dioxide and water. The implant is placed in the vitreous of the eye with a single-use applicator in a sutureless, office-based procedure. Treatment with a single dexamethasone intravitreal implant in patients with noninfectious intermediate or posterior uveitis has been shown to produce significant improvements in intraocular inflammation and best-corrected visual acuity with treatment benefit sustained for 6 months. Dexamethasone intravitreal implant has also been shown to reduce central retinal thickness and improve best-corrected visual acuity in patients with macular edema of various etiologies. The implant has been approved for treatment of noninfectious uveitis involving the posterior segment, diabetic macular edema, and macular edema associated with branch and central retinal vein occlusion.

  18. Visual Performance in Patients with Neovascular Age-Related Macular Degeneration Undergoing Treatment with Intravitreal Ranibizumab

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    Sarah Sabour-Pickett

    2013-01-01

    Full Text Available Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech in patients with neovascular age-related macular degeneration (nv-AMD. Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT was determined by optical coherence tomography (OCT. Results. Group mean (±sd MFT reduced significantly from baseline (233 (±59 to exit (205 (±40 (P=0.001. CDVA exhibited no change between baseline and exit visits (P=0.48 and P=0.31, resp.. Measures of visual function that did exhibit statistically significant improvements (P<0.05 for all included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS, mesopic and photopic glare disability (GD, and retinotopic ocular sensitivity (ROS at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.

  19. [Neurodevelopment in patients with retinopathy of prematurity treated with intravitreal bevacizumab. Case series].

    Science.gov (United States)

    Martínez-García, Sarah Melania; Hernández-Da Mota, Sergio Eustolio; Rubio-Rangel, Araceli; Rojas-Flores, Ignacio; Vieyra-López, Mayra Edith; Martínez-Castellanos, María Ana; Zavala-Martínez, María Teresa; Gómez García, Anel

    2017-01-19

    Retinopathy of prematurity (ROP) is an eye disease caused by an alteration in retinal vasculogenesis that may lead to partial or complete vision loss with a harmful impact in terms of neurodevelopment. The purpose of the present study was to determine the neurodevelopment in patients with type i retinopathy of prematurity treated with intravitreal bevacizumab. Case series. The inclusion criteria were: patients with type I ROP treated with a dose of 0.625mg/0.025ml of intravitreal bevacizumab. Demographic data and comorbidities were documented. Neurodevelopment was evaluated with the screening test of the Bayley Scale of Infant Development (BSID) in all patients between 11 and 28 weeks of age. Seven patients were included in the study. Four patients showed normal neurodevelopment according to the overall scores of the BSID scale. The distribution of high risk for neurodevelopmental delay in the different areas evaluated were as follows: 3 patients presented it in the cognitive area, one in the receptive communication area, one in the expressive area, one in the fine motor skills and 3 patients in the gross motor skills area. In these case series, the majority of patients treated with intravitreal bevacizumab for ROP showed normal neurodevelopment scores. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  20. Effectiveness of combined laser photocoagulation therapy with intravitreal anti -VEGF in Retinal arterial macroaneurysms: case report

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    Fernanda Pacella

    2014-12-01

    Full Text Available Background: Retinal arterial macroaneurysms (RAM is a pathological dilatation of retinal arterial vessel. Argon laser photocoagulation has been for a long time the gold standard of many vascular diseases of the retina such as macroaneurysm. From this work emerges how the introduction of intravitreal anti-VEGF therapies have enhanced the 'effectiveness of the combination of argon laser photocoagulation in cases of persistent retinal edema, we present the case of a retinal macroaneurysm with macular hemorrhage focus and oedema in a patient with a history of systemic arterial hypertension. Methods: A 77 year-old woman patient reported sudden decline in visual acuity in the left eye; the best corrected visual acuity (BCVAwas 1/10 in left eye. Fluorescein angiography (FAG resulted in diagnosis of Macroaneurysm at the posterior pole with macular hemorrhage focus and oedema. The patient was treated with laser treatment in the left eye; after 30 days, the visual acuity was 1/50 and at optical coherence tomography (OCT the retinal profile was significantly altered. After 30 days, a single intravitreal ranibizumab injection was performed and, after 7 days, visual acuity was 1/10. After 24 months from ranibizumab-based therapy the final visual acuity was 10/10 and OCT examination revealed a normal retinal profile. Conclusion: In this case report the association of argon laser photocoagulation with intravitreal anti-VEGF injection has been proven to be effective and safe in case of persistent retinal oedema.

  1. Clinical efficacy of intravitreal Ranibizumab in idiopathic choroid neovascularization type Ⅰand type Ⅱ

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    Yue-Ming Sun

    2015-07-01

    Full Text Available AIM: To evaluate the efficacy of intravitreal ranibizumab in idiopathic choroid neovascularization(ICNV, compare the difference of the curative effect between type Ⅰand Ⅱof ICNV by optical coherence tomography(OCT, further provide evidence of the to effectiveness of ranibizumab in the treatment of choroidal neovascularization to guide clinical treatment. METHODS: A retrospective analysis on the clinical data who were diagnosed as ICNV between October 2013 and June 2014 in our hospital were carried out. Totally 31 cases(9 cases of type Ⅰ and 22 cases of type Ⅱaccepted ranibizumab injection voluntarily.All of the patients were evaluated by ophthalmic examination, funduscopy and OCT before and after the injection, classificated according to OCT results. The best-corrected visual acuity(BCVAand maximum of edema thickness after ranibizumab treatment at 3mo follow-up were compared. RESULTS: After statistically analyzed, BCVA and maximum thickness of the retinal lesions of 31 patients(type Ⅰ9 cases, type Ⅱ 22 casesbefore and 1, 3mo after treatment had statistical significance. In different types of retinal ICNV patients, BCVA and maximum thickness of the retinal lesions before and after treatment had no statistical significance. It was said that ranibizumab intravitreal injection had effectiveness for ICNV, however, there were no significant effectiveness for typeⅠ andⅡ ICNV. CONCLUSION: Ranibizumab intravitreal injection has obvious effectiveness for ICNV. However, it has no effect on typeⅠ andⅡ ICNV. Its safety and long-term complications need for further study.

  2. Efficacy of intravitreal Ranibizumab injection for choroidal neovascularization secondary to pathologic myopia

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    Li-Hong Cui

    2016-03-01

    Full Text Available AIM:To observe the efficacy and safety of intravitreal Ranibizumab injection in patiens with choroidal neovascularization(CNVsecondary to pathologic myopia.METHODS:In this retrospective and comparative study,24 patients(25 eyeswith CNV secondary to pathologic myopia were enrolled. All patients were assessed by examinations of ETDRS visual acuity chart, preplaced-mirror ophthalmoscopy, fundus fluorescein angiography(FFA, indocyanine green angiography(ICGAand optical coherence tomography(OCT. Patiens received intravitreally injected ranibizumab 0.5mg(0.05mL. Treatments were repeated if the follow-up indicated that it was necessary. The follow-up periods were 4~10mo. Best corrected visual acuity(BCVA, central macular thickness(CMTand leakage of CNV before and after the treatment were compared. RESULTS:No local or systemic complications occurred in any patients during the treatment or follow-up. The average time of injection was 1.52. The mean BCVA was 23.93±12.46 letters before the therapy. In the last follow-up, the mean BCVA was 40.63±7.25 letters, improved by 14.27±9.36 letters and the difference was statically significant(t=5.74, Pt=3.96, PCONCLUSION:Intravitreal ranibizumab injection for CNV secondary to pathologic myopia is safe and effective, and this treatment can improve visual acuity, reduce retina edema and leakage of CNV.

  3. Visual performance in patients with neovascular age-related macular degeneration undergoing treatment with intravitreal ranibizumab.

    Science.gov (United States)

    Sabour-Pickett, Sarah; Loughman, James; Nolan, John M; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.

  4. Effect of photodynamic therapy combined with intravitreal ranibizumab injection on circumscribed choroidal hemangioma

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    Yu-Shun Xue

    2017-02-01

    Full Text Available AIM:To investigate the effect of photodynamic therapy(PDTcombined with intravitreal injection of ranibizumab on circumscribed choroidal hemangioma(CCH. METHODS:A retrospective study was performed for 6 eyes(6 casesdiagnosed as CCH. Before treatment, OCT examination showed macular cystoid edema and retinal neurepithelium layer detachment in all patients. All patients underwent photodynamic therapy, then intravitreal injection of ranibizumab 0.5mg(0.05mLwere administered at 48h after PDT. The best corrected visual acuity(BCVA, examination of the ocular fundus, fundus photography, fluorescence fundus angiography(FFA, indocyanine green angiography(ICGA, eye B ultrasonic and optical coherence tomography(OCTwere performed respectively at 1, 3 and 6mo after treatment. RESULTS:The patients were followed up for 4 to 10mo, the final vision of follow-up increased than before, it was raised 7 lines. The images of ICGA revealed hypofluorescence or no leakage in focal area. Eye B ultrasonic showed that hemangioma shrunk or faded. The images of ICGA revealed macular region retinal reattached well and edema disappeared completely. Mean flow-up was 6mo postoperative. There had no evidence of recurrence. CONCLUSION:For CCH patients, hemangioma got smaller obviously by PDT. Intravitreal ranibizumab injection promote effusion absorption under the retina. Combining use of the two therapies could improve visual acuity in a short-term.

  5. Effect of photodynamic therapy combined with intravitreal injection of Lucentis therapy on choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei Su

    2016-01-01

    Objective:To analyze the efficacy of photodynamic therapy combined with intravitreal injection of Lucentis therapy for choroidal neovascularization.Methods: A total of 82 cases with choroidal neovascularization receiving inpatient therapy in our hospital from August 2013 to August 2014 were selected as research subjects, and according to random number table method, all enrolled patients were divided into control group (received photodynamic therapy) and observation group (received photodynamic therapy combined with intravitreal injection of Lucentis therapy), each group with 41 cases. Differences in best corrected visual acuity, intraocular pressure and central macular thickness, mean sensitivity of visual field and so on of two groups were compared.Results:After treatment, visual acuity improvement ratio of observation group was significantly higher than that of control group and visual acuity decrease ratio was lower than that of control group (P<0.05); intraocular pressure and central macular thickness were significantly less than those of control group (P<0.05); mean sensitivity of 10o and 30o visual field was higher than that of control group (P<0.05).Conclusions:Photodynamic therapy combined with intravitreal injection of Lucentis therapy can effectively improve vision and visual acuity of patients with choroidal neovascularization and reduce intraocular pressure and central macular thickness; it is an ideal treatment method.

  6. Bilateral Intravitreal Dexamethasone Implant for Retinitis Pigmentosa-Related Macular Edema

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    Ali Osman Saatci

    2013-03-01

    Full Text Available Purpose: To report the efficacy of intravitreal dexamethasone implant in a patient with retinitis pigmentosa and bilateral cystoid macular edema unresponsive to topical carbonic anhydrase inhibitors. Case Report: A 36-year-old man with bilateral cystoid macular edema associated with retinitis pigmentosa that was unresponsive to topical carbonic anhydrase inhibitors underwent bilateral 0.7-mg intravitreal dexamethasone implants two weeks apart. Spectral domain optical coherence tomography revealed resolution of macular edema one week following each injection in both eyes and his visual acuity improved. However, macular edema recurred two months later in OS and three months later in OD. Second implant was considered for both eyes. No implant-related complication was experienced during the follow-up of seven months. Conclusion: Inflammatory process seems to play a role in retinitis pigmentosa. Intravitreal dexamethasone implant may offer retina specialists a therapeutic option especially in cases unresponsive to other treatment regimens in eyes with retinitis pigmentosa-related macular edema.

  7. Long-Term Follow-Up of Intravitreal Bevacizumab in Retinal Arterial Macroaneurysm: A Case Report

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    Shani Golan

    2011-12-01

    Full Text Available Purpose: To present the long-term effect of intravitreal bevacizumab (Avastin® therapy in a patient suffering from retinal arterial macroaneurysm. Methods: Case report of a 72-year-old female diagnosed with retinal macroaneurysm in the superior temporal artery leading to macular edema. Functional and morphological data at baseline, 4 weeks, 2 months, and 13 months following treatment with two consecutive intravitreal bevacizumab injections are presented. Results: Best-corrected visual acuity improved from 20/160 at baseline to 20/20 at the3-months follow-up and remained stable through 13 months of follow-up. Central retinal thickness measured by optical coherence tomography decreased from 364 µm at baseline to 248 µm at the 13-months follow-up. No ocular or systemic side effects were detected. Conclusions: Intravitreal bevacizumab therapy may lead to resolution of macular edema associated with retinal macroaneurysm and consequently visual improvement. This treatment may promise a long-lasting effect but warrant further investigation in larger series.

  8. Patients' tolerance of bimanual lid retraction versus a metal speculum for intravitreal injections

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    Alattas K

    2016-09-01

    Full Text Available Khadijah Alattas Department of Ophthalmology, College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia Objective: To compare patients’ acceptance of and correlate their pain level for bimanual versus metal speculum fixation in intravitreal injections. Design: Prospective analysis. Participants: Seventy-three eyes of 56 patients. Methods: A questionnaire indicating patients’ discomfort and pain grading immediately after intravitreal injections using either bimanual fixation or metal speculum fixation (Barraquer Wire Speculum. Results: Fifty-six patients who underwent intravitreal injections were enrolled in this study for various conditions. Patients’ overall pain and discomfort were as follows, right eye – bimanual was 0.3 on our grading scale with a standard deviation of 0.54, right eye – metal was 1.6 on our grading scale with a standard deviation of 1.5, left eye – bimanual was 0.41 on our grading scale with a standard deviation of 0.87, and left eye – metal was 1.91 on our grading scale with a standard deviation of 1.14 (P=0.003. Conclusion: Patients who underwent bimanual fixation had a much more comfortable experience with less pain in comparison to patients who underwent metal speculum fixation. Keywords: AMD, diabetic retionpathy, Avastin, eye injection

  9. Predictive factors for functional improvement following intravitreal bevacizumab injections after central retinal vein occlusion.

    Science.gov (United States)

    Januschowski, Kai; Feltgen, Nicolas; Pielen, Amelie; Spitzer, Bernhard; Rehak, Matus; Spital, Georg; Dimopoulos, Spyridon; Meyer, Carsten H; Szurman, Gesine B

    2017-03-01

    Vision loss in central retinal vein occlusion (CRVO) is mostly caused by macular edema (ME) and can be treated with intravitreal bevacizumab injections. The goal of this study was to identify predictive factors for improvement in visual acuity. Three hundred and sixteen eyes of six centres having received intravitreal bevacizumab for ME due to CRVO were enrolled in this multicentre, retrospective, interventional case series. The follow-up time was 24 to 48 weeks. Investigated patient characteristics were pretreatment, duration of CRVO prior to the first injection, initial best-corrected visual acuity (BCVA), baseline central retinal thickness as measured by optical coherence tomography, gender, eye, age, comorbidity with glaucoma, systemic hypertension, or diabetes mellitus. Multiple regression analysis confirmed the following baseline predictive factors for an increase in visual acuity: low BCVA (p  0.1). Intravitreal injections of bevacizumab in a routine clinical setting effectively improved and stabilized BCVA in CRVO. Our large multicenter study identified initial BCVA, baseline CRT, and pre-treatment as prognostic factors for visual improvement.

  10. Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons

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    Andy A. Yanez

    2017-02-01

    Full Text Available Herpes simplex viruses (HSV1 and HSV2 establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs. Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG and sympathetic superior cervical ganglia (SCG after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons.

  11. NGF and HB-EGF: potential biomarkers that reflect the effects of fesoterodine in patients with overactive bladder syndrome.

    Science.gov (United States)

    Kim, Soo Rim; Moon, Yeo Jung; Kim, Sei Kwang; Bai, Sang Wook

    2015-01-01

    To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls (pfesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13±0.08 pg/mg; 16 weeks: 0.60±0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73±6.55 pg/mg; 16 weeks: 4.72±2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (pfesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.

  12. Seminal plasma proteomic and gene expression and ngf location and receptors (TRK1 and NGFR) in rabbit genital system

    OpenAIRE

    JÃsy Maria Arruda de Alencar

    2015-01-01

    The aim this study were (i) to map and identify proteins in seminal plasma of New Zealand white rabbits strain, using the techniques of two-dimensional electrophoresis coupled to mass spectrometry and to estimate associations between these proteins with sperm parameters and (ii) characterize expression of the nerve growth factor polypeptide beta ( -NGF) and its cognate neurotrophic receptor tyrosine kinase type 1 (NTRK1), and nerve growth factor receptor (NGFR) at gonads and sex glands in adu...

  13. Chemoenzymatically prepared konjac ceramide inhibits NGF-induced neurite outgrowth by a semaphorin 3A-like action

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    Seigo Usuki

    2016-03-01

    Full Text Available Dietary sphingolipids such as glucosylceramide (GlcCer are potential nutritional factors associated with prevention of metabolic syndrome. Our current understanding is that dietary GlcCer is degraded to ceramide and further metabolized to sphingoid bases in the intestine. However, ceramide is only found in trace amounts in food plants and thus is frequently taken as GlcCer in a health supplement. In the present study, we successfully prepared konjac ceramide (kCer using endoglycoceramidase I (EGCase I. Konjac, a plant tuber, is an enriched source of GlcCer (kGlcCer, and has been commercialized as a dietary supplement to improve dry skin and itching that are caused by a deficiency of epidermal ceramide. Nerve growth factor (NGF produced by skin cells is one of the itch factors in the stratum corneum of the skin. Semaphorin 3A (Sema 3A has been known to inhibit NGF-induced neurite outgrowth of epidermal nerve fibers. It is well known that the itch sensation is regulated by the balance between NGF and Sema 3A. In the present study, while kGlcCer did not show an in vitro inhibitory effect on NGF-induced neurite outgrowth of PC12 cells, kCer was demonstrated to inhibit a remarkable neurite outgrowth. In addition, the effect of kCer was similar to that of Sema 3A in cell morphological changes and neurite retractions, but different from C2-Ceramide. kCer showed a Sema 3A-like action, causing CRMP2 phosphorylation, which results in a collapse of neurite growth cones. Thus, it is expected that kCer is an advanced konjac ceramide material that may have neurite outgrowth-specific action to relieve uncontrolled and serious itching, in particular, from atopic eczema.

  14. Filamentous fungal endophthalmitis: results of combination therapy with intravitreal amphotericin B and voriconazole

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    Mithal K

    2015-04-01

    Full Text Available Kopal Mithal,1 Avinash Pathengay,1 Abhishek Bawdekar,1 Animesh Jindal,1 Divya Vira,2 Nidhi Relhan,3 Himadri Choudhury,1 Namrata Gupta,1 Varun Gupta,1 Nagendra K Koday,4 Harry W Flynn Jr3 1Retina and Uveitis Services, 2Cornea Services, LV Prasad Eye Institute, GMR Varalakshmi Campus, Visakhapatnam, India; 3Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 4Ocular Microbiology Service, LV Prasad Eye Institute, GMR Varalakshmi Campus, Visakhapatnam, India Purpose: To report outcomes of exogenous fungal endophthalmitis treated with combination of intravitreal antifungal agents. Design: Retrospective, non-randomized, interventional, consecutive case series. Methods: Twelve eyes of twelve consecutive cases of filamentous fungal endophthalmitis were treated with a combination of intravitreal amphotericin-B and intravitreal voriconazole (AmB-Vo Regime along with pars plana vitrectomy at a single center. Clinical characteristics, microbiology results, treatment strategy, visual, and anatomical outcomes were analyzed. Results: Ten cases out of the twelve were postoperative endophthalmitis of which nine were part of a post cataract surgery cluster. The remaining included endophthalmitis following keratitis post pterygium excision (1 and following open globe injury (2. The most common fungus was Aspergillus terreus, which was isolated in 8/12, followed by A. flavus in 2/12 and Fusarium solani in 1/12. The presenting visual acuity ranged from light perception (LP to counting fingers. The visual acuity at final follow-up was 20/400 or better in 7/12 eyes (58.33% and 20/60 in 2/12 eyes (range 20/60 to LP. All eyes with corneal involvement had final visual acuity 20/400 or worse. Globe salvage was achieved in all cases. Conclusion: Combining intravitreal amphotericin-B and voriconazole could be a novel treatment strategy in the management of endophthalmitis caused by filamentous fungus. Eyes

  15. Intravitreal bevacizumab injection in the treatment of macular edema secondary to branch retinal vein occlusion

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    Şeref İstek

    2014-06-01

    Full Text Available AIM:To evaluate the 12mo results of intravitreal bevacizumab injection on central macular thickness(CMTand visual acuity in the treatment of macular edema(MEsecondary to branch retinal vein occlusion(BRVO.METHODS:Thirty-two patients who underwent intravitreal bevacizumab(Altuzan®0.125mg/0.05mL injection for ME secondary to BRVO at least 12mo follow up period have been studied respectively. Patients with diagnosis of ME secondary to BRVO were applied an ophthalmic examination, CMT measurement, and fluorescein angiography, so patients whose CMT above 250μm were offered intravitreal bevacizumab treatment. Patients who had macular ischemia on fluorescein angiography, neovascularisation elsewhere secondary to other types of diseases, received any intraocular treatment before(such as laser treatment, intravitreal injection or eye surgeryhave been out of trial. Data of logMAR best corrected visual acuity(BCVAand CMT in control visits have been evaluated. For statistical analysis Student's paired t-test was used by Minitab15.0 software and a P-value RESULTS: Mean logMAR BCVA changes and mean CMT changes were statistically significant compared to pre-injection values at last visit(P0.01. Mean BCVA increment was 0.477±0.235, mean CMT decline was 257.906±88.865 compared to pre-injection at last visit. Ten(31%of the patients had a positive response with a single injection and no recurrence of ME for a mean of 12.6±0.66mo. Five(15.6%patients received injection two times and 17(53%patients more than 3 injections. Mean injection per eye was 2.18±0.91(1~4respectively. Recurrence of ME was seen aproximately in 2.45±0.63mo at the first control, 2.58±0.66mo at the second control and 3.17±0.48mo at the third control respectively. Five(15.6%of the patients needed multiple injections for reducing ME whereas visual acuity gain was not achieved as ME reduced in those patients. CONCLUSION: Treatment of ME secondary to BRVO with intravitreal bevacizumab seems

  16. Clinical efficacy and effect of mNGF on inflammatory factor and oxidative stress in patients with severe intracerebral hemorrhage

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    Fang Li; Lu Wang; Mutalifu-Maihemuti; Dong Xiao

    2016-01-01

    Objective:To investigate the effect of mouse nerve growth factor (mNGF) on inflammatory factors and oxidative stress in patients with severe intracerebral hemorrhage.Methods:A total of 84 severe intracerebral hemorrhage patients were randomly divided into observation group (42 cases) and control group (42 cases). The two groups were given the conventional therapy of controlling intracranial pressure and glucose, and the observation group was additionally given mNGF. The efficacy in the two groups was observed. The levels of inflammatory factors including hs-CRP, IL-8 and TNF-α and oxidative stress indicators including malondialdehyde (MDA) and superoxide dismutase (SOD) were tested before and after treatment and compared in the two groups. Results:Total effective rate was significantly increased after treatment in observation group; compared with before treatment, the levels of hs-CRP, IL-8 and TNF-ααwere significantly reduced after treatment in the two groups, and more significantly decreased in the observation group; compared with before treatment, the levels of MDA and SO were significantly reduced after treatment in the two groups, and more significantly decreased in the observation group.Conclusion:The mNGF treatment has reliable curative effect in severe intracerebral hemorrhage patients, which can improve inflammatory response and oxidative stress.

  17. 重组EpoAB-NGF模拟肽的神经营养功能%Preliminary Study on Neurotrophic Activity of Recombinant Peptide Mimics EpoAB-NGF

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    潘勇昭; 陈虹; 王欣; 马晓骊; 黄秉仁

    2011-01-01

    Objective: To investigate the neurotrophic activity of recombinant fusion protein epopeptide ABnerve growth factor analog peptide (EpoAB-NGF9/12). Methods: The DNA fragments encoding the sequences of EpoAB-NGF9 and EpoAB-NGF12 polypeptide were amplified by PCR and cloned into the pET-42a prokaryotic expression vector. The recombinant plasmids of pET-42a-EpoAB-NGF9/12 were transformed into E. coli BL21 (DE3) and exogenous protein expression was induced by IPTG. Fusion proteins GST-EpoAB-NGF9/12 were purified by affinity chromatography. The biological activities were determined using the experiment of inducing axon outgrowth of PC12 cells and flow cytometry analysis of apoptotic rate in R2L1 cells. Results: Apparent molecular weight of fusion proteins GST-EpoAB-NGF9/12 were approximate 30kDa. Immunoblot analysis showed that the fusion proteins were immunoreactive with anti-GST antibody. Fusion proteins stimulate the differentiation and promote the axon outgrowth in PC12 cells. Cell apoptosis was induced in (31.7 ±0.60)% of R2L1 control cells by serum free incubation, whereas cell apoptosis rate were in ( 25.2 ± 3.52 ) % or ( 25.7 ± 1.46 ) % by adding GST-EpoAB-NGF9 or GST-EpoAB-NGF12 into serum free condition respectively. The result indicates that fusion proteins were enabling to prevent cell death in R2L1 cells. Conclusion: These findings in cell biology region suggest that recombinant fusion protein containing Epo-NGF peptide mimics have the neurotrophic effects similar to that of NGF.%目的:研究重组融合蛋白红细胞生成素AB肽-神经生长因子模拟肽(EpoAB-NGF9和EpoAB-NGF/12)的神经营养作用.方法:构建pET-42a-EpoAB-NGF9/12原核表达质粒,转化大肠杆菌BL21(DE3),以IPTG诱导表达,亲和层析纯化重组蛋白,显微镜观察PC12细胞诱导分化,流式细胞仪检测凋亡细胞.结果:大肠杆菌表达的重组融合蛋白GST-EpoAB-NGF9/12分子量约为30kDa,抗GST抗体免疫印迹反应呈阳

  18. Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF: effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion

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    Patwardhan Amol M

    2005-01-01

    Full Text Available Abstract Background Nerve growth factor (NGF, glial cell line-derived neurotrophic factor (GDNF and brain-derived neurotrophic factor (BDNF all play important roles in the development of the peripheral sensory nervous system. Additionally, these growth factors are proposed to modulate the properties of the sensory system in the adult under pathological conditions brought about by nerve injury or inflammation. We have examined the effects of NGF, GDNF and BDNF on adult rat trigeminal ganglion (TG neurons in culture to gain a better understanding of how these growth factors alter the cytochemical and functional phenotype of these neurons, with special attention to properties associated with nociception. Results Compared with no growth factor controls, GDNF, at 1 and 100 ng/ml, significantly increased by nearly 100% the number of neurons in culture at 5 days post-plating. A significant, positive, linear trend of increasing neuron number as a function of BDNF concentration was observed, also peaking at nearly 100%. NGF treatment was without effect. Chronic treatment with NGF and GDNF significantly and concentration-dependently increased 100 nM capsaicin (CAP-evoked calcitonin gene-related peptide (CGRP release, reaching approximately 300% at the highest concentration tested (100 ng/ml. Also, NGF and GDNF each augmented anandamide (AEA- and arachidonyl-2-chloroethylamide (ACEA-evoked CGRP release, while BDNF was without effect. Utilizing immunohistochemistry to account for the proportions of TRPV1- or CGRP-positive neurons under each growth factor treatment condition and then standardizing evoked CGRP release to these proportions, we observed that NGF was much more effective in enhancing CAP- and 50 mM K+-evoked CGRP release than was GDNF. Furthermore, NGF and GDNF each altered the concentration-response function for CAP- and AEA-evoked CGRP release, increasing the Emax without altering the EC50 for either compound. Conclusions Taken together, our

  19. Pneumatic displacement and intravitreal bevacizumab: A new approach for management of submacular hemorrhage in choroidal neovascular membrane

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    Chawla Shobhit

    2009-01-01

    Full Text Available Choroidal neovascular membrane (CNVM is one of the most common causes of submacular hemorrhage (SMH. Conventional treatment involves management of the SMH with pneumatic displacement with or without tissue plasminogen activator (TPA followed by intravitreal injection of bevacizumab in a second sitting. We decided to assess the efficacy of treating SMH secondary to CNVM with pneumatic displacement using sulphur hexafluoride (SF6 gas and intravitreal bevacizumab. Four patients with SMH secondary to CNVM were included in this study. Intravitreal bevacizumab, 0.05 ml, along with 0.5 ml of SF6 was injected through the pars plana into the vitreous cavity. Postoperative best corrected visual acuity improved in all eyes with complete or partial displacement of SMH out of the foveal area.

  20. Surgical removal of retained subfoveal perfluorocarbon liquid through a therapeutic macular hole with intravitreal PFCL injection and gas tamponade.

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    Kim, Jae Min; Woo, Se Joon; Park, Kyu Hyung; Chung, Hum

    2013-10-01

    We report two cases of surgical removal of a retained subfoveal perfluorocarbon liquid (PFCL) bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade. Two patients underwent pars plana vitrectomy with PFCL injection for rhegmatogenous retinal detachment. In both cases, a retained subfoveal PFCL bubble was noticed postoperatively by funduscopy and optical coherence tomography. Both patients underwent surgical removal of the subfoveal PFCL through a therapeutic macular hole and gas tamponade. The therapeutic macular holes were completely closed by gas tamponade and the procedure yielded a good visual outcome (best-corrected visual acuity of 20 / 40 in both cases). In one case, additional intravitreal PFCL injection onto the macula reduced the size of the therapeutic macular hole and preserved the retinal structures in the macula. Surgical removal of a retained subfoveal PFCL bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade provides an effective treatment option.

  1. Adult Coats’ Disease Successfully Managed with the Dexamethasone Intravitreal Implant (Ozurdex® Combined with Retinal Photocoagulation

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    Sebastián Martínez-Castillo

    2012-03-01

    Full Text Available Purpose: To report a case of Coats’ disease managed with the dexamethasone intravitreal implant Ozurdex® (Allergan, Inc., Irvine, Calif., USA combined with retinal photocoagulation. Methods: A 46-year-old female with 20/200 visual acuity was diagnosed with Coats’ disease with secondary retinal vasoproliferative tumor. An initial approach was performed with an intravitreal injection of the sustained-release dexamethasone implant Ozurdex. After reattachment of the retina, the telangiectatic vessels were treated with laser photocoagulation. Results: The patient’s visual acuity improved to 20/25 after the intravitreal Ozurdex. No further recurrences of exudation were evident through the 12-month follow-up. Conclusions: Ozurdex may be an effective initial therapeutic approach for Coats’ disease with immediate anatomical response and visual improvement.

  2. Long-Term Follow-Up of Intravitreal Ranibizumab for the Treatment of Choroidal Neovascularization due to Choroidal Osteoma

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    Zenith H.Y. Wu

    2012-06-01

    Full Text Available Choroidal osteoma is an uncommon benign osseous intraocular tumor that typically affects young adult women. Choroidal neovascularization (CNV is one of the complications that can develop in eyes with choroidal osteoma. We present a case of CNV secondary to choroidal osteoma treated with intravitreal ranibizumab. A 57-year-old lady presented with painless loss of vision with a right-eye visual acuity of 20/800. Fundus examination showed a well-demarcated yellowish peripapillary choroidal osteoma with associated retinal and subretinal hemorrhage due to CNV. Three intravitreal ranibizumab injections at monthly intervals were given and her visual acuity improved to 20/30 following treatment. After 1.2 years of follow-up, the right eye visual acuity was maintained at 20/30 with no evidence of CNV recurrence. Our findings suggest that intravitreal ranibizumab may be an effective therapeutic option for treating CNV secondary to choroidal osteoma.

  3. Contralateral eye-to-eye comparison of intravitreal ranibizumab and a sustained-release dexamethasone intravitreal implant in recalcitrant diabetic macular edema

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    Thomas BJ

    2016-08-01

    Full Text Available Benjamin J Thomas, Yoshihiro Yonekawa, Jeremy D Wolfe, Tarek S Hassan Department of Vitreoretinal Surgery, William Beaumont Hospital, Royal Oak, MI, USA Objective: To compare the effects of intravitreal ranibizumab (RZB or dexamethasone (DEX intravitreal implant in cases of recalcitrant diabetic macular edema (DME.Methods: Retrospective, interventional study examining patients with symmetric bilateral, center-involved DME recalcitrant to treatment with RZB, who received DEX in one eye while the contralateral eye continued to receive RZB every 4–5 weeks for a study period of 3 months.Results: Eleven patients (22 eyes were included: mean logarithm of the minimal angle of resolution (logMAR visual acuity (VA for the DEX arm improved from 0.415 (standard deviation [SD] ±0.16 to 0.261 (SD ±0.18 at final evaluation, and mean central macular thickness (CMT improved from 461 µm (SD ±156 to 356 µm (SD ±110; net decrease: 105 µm, P=0.01. Mean logMAR VA for the RZB arm improved from 0.394 (SD ±0.31 to 0.269 (SD ±0.19 at final evaluation. Mean CMT improved from 421 µm (SD ±147 to 373 µm (SD ±129; net decrease: 48 µm, P=0.26.Conclusion: A subset of recalcitrant DME patients demonstrated significant CMT reduction and VA improvement after a single DEX injection. Keywords: aflibercept, bevacizumab, central macular thickness, macular edema, dexamethasone implant, diabetic macular edema, diabetic retinopathy, ranibizumab

  4. Intravitreal Expansile Gas and Bevacizumab Injection for Submacular Hemorrhage Due to Neovascular Age-related Macular Degeneration

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    Ramin Nourinia

    2010-01-01

    Full Text Available Purpose: To evaluate the results of intravitreal expansile gas injection, with or without recombinant tissue plasminogen activator (rtPA, followed by intravitreal bevacizumab injection for treatment of submacular hemorrhage (SMH secondary to neovascular age-related macular degeneration (AMD. Methods: In this interventional case series, 5 eyes of 5 patients with SMH secondary to choroidal neovascularization (CNV due to neovascular AMD were treated with 0.3 cc intravitreal SF6 (and 50 μg of rtPA in two eyes, followed by face-down positioning; 24 hours later, 1.25 mg of bevacizumab was injected intravitreally. Main outcome measures included displacement of SMH and best corrected visual acuity (BCVA. Results: Mean patient age was 75.6±9.2 (range, 60-83 years, mean duration of symptoms was 6.4±3.2 (range, 3-10 days, and mean number of bevacizumab injections was 1.8 (range, 1-3. Mean preoperative BCVA was 1.28±0.27 logMAR which improved significantly to 0.57±0.33 logMAR at 12 months (P=0.042. SMH displacement occurred in all eyes, and visual acuity improved and remained stable during the follow-up period of 12 months. Conclusion: Intravitreal expansile gas injection, with or without rtPA, followed by intravitreal bevacizumab injection, seems to be an effective modality for SMH displacement and treatment of the underlying CNV in neovascular AMD.

  5. Intravitreal bevacizumab as primary treatment for retinal angiomatous proliferation: twelve-month results.

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    Gharbiya, Magda; Allievi, Francesca; Recupero, Vincenzo; Martini, Delia; Mazzeo, Luigi; Gabrieli, Corrado Balacco

    2009-06-01

    To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of retinal angiomatous proliferation. Seventeen eyes from 16 patients with newly diagnosed retinal angiomatous proliferation underwent intravitreal injections of bevacizumab, 1.25 mg. The patients were scheduled for three monthly bevacizumab injections. Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, central macular thickness on optical coherence tomography, and fluorescein angiographic findings were examined before and after treatment. Patients were followed-up for 12 months. The mean best-corrected visual acuity (+/- standard deviation [SD]) at baseline was 39.53 (+/-10.40) letters (Snellen equivalent: 20/42). At 12 months after treatment the mean best-corrected visual acuity (+/-SD) improved significantly (P = 0.0000001) to 47.88 (+/-11.78) letters (Snellen equivalent: 20/28). Best-corrected visual acuity improved 3 ETDRS lines or more in 3 (17.65%) of 17 treated eyes, 14 (82.35%) eyes were stable, and 15 (88.23%) eyes gained 1 or more ETDRS lines. The mean central macular thickness (+/-SD) at baseline was 297 (+/-60.72) microm. At 12 months after treatment, the mean central macular thickness (+/-SD) reduced significantly (P = 0.00001) to 237 (+/-28.80) microm. At the 12-month follow-up, absence of fluorescein leakage was demonstrated in 14 (82%) of 17 treated eyes. No ocular or systemic adverse effects from treatment were encountered. The 12-month results of intravitreal bevacizumab for retinal angiomatous proliferation are very promising with no apparent short-term safety concerns. Treated eyes had a significant functional and anatomical improvement. Further studies will be needed to better determine long-term efficacy and safety.

  6. Intravitreal bevacizumab (Avastin in the treatment of macular edema secondary to retinal vein occlusion

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    Juan Carlos Mesa Gutiérrez

    2008-09-01

    Full Text Available Juan Carlos Mesa Gutiérrez, Luis Arias Barquet, Josep Maria Caminal Mitjana, Sergi Prades Almolda, Nùria Planas Domènech, Octavi Pujol Goita, Marc Rubio Caso, Jorge Arruga GinebredaDepartment of Ophthalmology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, SpainObjective: To evaluate efficacy and safety of intravitreal injections of bevacizumab in the treatment of macular edema secondary to retinal vein occlusion (RVO.Methods: Prospective study, noncomparative, interventional case series. Twelve consecutive patients (12 eyes with macular edema associated with nonischemic retinal vein occlusion were treated with intravitreal bevacizumab (1.25 mg. All subjects underwent standardized ophthalmic evaluation at baseline and at weeks 1, 4, 12, and 24, consisting of visual acuity (VA measurement using ETDRS charts, and imaging with ocular coherence tomography evaluating changes in foveal thickness (FT and macular volume (MV.Results: The median age was 66 years (± 4.16, and the median duration of symptoms was 4 months (± 1.81. There were six cases of inferior branch vein occlusion and six cases of superior branch retinal vein occlusion. Mean VA improved from 1.32 ± 0.24 (logMAR values at baseline to 0.8 ± 0.15 (p = 0.0003 at the 6-month follow-up. The macular edema responded promptly, and a trend to restoration of normal macular anatomy was observed at by the seventh day. Mean FT improved from 615.50 ± 116.29 microns to 420 ± 72.53 microns (p = 0.001, and the mean MV improved from 19.81 ± 2.31mm3 to 9.23 ± 1.38 (p = 0.0001 at the 6-month follow-up.Keywords: Bevacizumab, retinal vein occlusion, intravitreal injection, vascular endothelial growth factor

  7. Biocompatible reverse thermal gel sustains the release of intravitreal bevacizumab in vivo.

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    Rauck, Britta M; Friberg, Thomas R; Medina Mendez, Carlos A; Park, Daewon; Shah, Veeral; Bilonick, Richard A; Wang, Yadong

    2014-01-23

    We assessed the in vivo release profile of bevacizumab from and biocompatibility of poly(ethylene glycol)-poly-(serinol hexamethylene urethane), or ESHU, a thermoresponsive hydrogel administered intravitreally for drug delivery. The technical feasibility of injection was assessed quantitatively via mechanical testing. For in vivo studies, New Zealand White rabbit eyes were injected intravitreally with 0.05 mL of either: ESHU dissolved in 25 mg/mL bevacizumab, ESHU dissolved in PBS, or 25 mg/mL bevacizumab. Clinical examination included IOP measurements and examination with indirect ophthalmoscopy for signs of inflammation. Additionally, eyes were examined histologically following euthanasia. To quantify bevacizumab release, aqueous humor samples were obtained via anterior chamber paracentesis and ELISA was used to determine the concentration of drug weekly. In vitro cytotoxicity testing also was performed using bovine corneal endothelial cells. The ESHU was injected easily through a 31-gauge needle, was well tolerated in vivo, and caused minimal cell death in vitro when compared to other common materials, such as silicone oil. The long-term presence of the gel did not affect IOP, and there was no evidence of inflammation histologically or through indirect observation. The ESHU sustained the release of bevacizumab for over 9 weeks and maintained a drug concentration that averaged 4.7 times higher than eyes receiving bolus bevacizumab injections. To our knowledge, this is the first report demonstrating sustained bevacizumab release in vivo from an intravitreally injected hydrogel formulation, suggesting that this delivery system may be a promising candidate for ocular drug delivery.

  8. Results of the treatment with intravitreal bevacizumab injection in branch retinal vein occlusion

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    Osman Sayýn

    2017-06-01

    Material and Method: The files of patients who had macular edema caused by branch retinal vein occlusion and who were applied intravitreal bevacizumab injection were studied retrospectively. Visual acuity (logMAR in follow-ups of the patients before and after the injection and the macular thickness values of the quadrant of the occlusion were recorded and the effect of intravitreal bevacizumab on these parameters were analyzed. Results: 24 eyes of 24 patients, 17 of which are male and 7 of which are female, were included in the study. The mean age of the patients were 59.1±7.7. The mean visual acuity prior to the injection was determined to be 0.7±0.5 logMAR, and the mean macular thickness value 489.7±129.6 μm. The mean injection number applied was 1.5±0.7. The mean follow-up time after the injection was 3.5±2.7 months. The mean macular thickness was determined to be 393.1±5.7 μm and mean visual acuity was 0.5±0.1 logMAR in the 1st month. In the last follow-ups of the patients, the mean visual acuity was 0.26±0.28 logMAR and the mean macular thickness value was 317.4±71.5 μm. The increase in visual acuity and decrease in macular thickness between first and last control after the injection was found statistically significant. (p<0.001. Conclusion: The intravitreal bevacizumab injection used in macular edema secondary to BRVO increases visual acuity and decreases macular thickness. [J Contemp Med 2017; 7(2.000: 143-148

  9. Results of Intravitreal Ranibizumab Treatment for Exudative Age-Related Macular Degeneration

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    Umut Karaca

    2012-01-01

    Full Text Available Pur po se: To evaluate the efficacy and safety of intravitreal ranibizumab injection for exudative age-related macular degeneration. Ma te ri al and Met hod: In this study, we included forty-eight eyes of 43 age-related macular degeneration patients followed for at least twelve months. Mean age was 73.65±8.93 years and mean follow-up time was 14.2 months. All patients received three consecutive monthly intravitreal ranibizumab injections and then were followed up with clinical examination and optic coherence tomography monthly. Re-injection was executed as needed. Re sults: Twenty patients were male (46.5% and twenty-three patients were female (53.5%. The average number of ranibizumab injection was 3.7 (3-7 per eye. Twenty-six lesions (54.2% were classic (predominantly and minimally and twenty-two (45.8% were occult. Mean best-corrected visual acuity was 46.8 letters with ETDRS chart at the initial examination and 55.5 letters at twelfth month. Mean central foveal thickness decreased from 320 microns to 269 microns. There was a statistically significant improvement in visual acuity and central foveal thickness. On the other hand, this improvement was not significant between lesion types. During follow-up, there were no systemic or serious ocular complications determined. Dis cus si on: Intravitreal ranibizumab injection is safe and effective, both anatomically and functionally, for age-related macular degeneration. (Turk J Ophthalmol 2012; 42: 25-9

  10. The combination of intravitreal triamcinolone and phacoemulsification surgery in patients with diabeticfoveal oedema and cataract

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    Cannon Paul S

    2005-06-01

    Full Text Available Abstract Background The management of diabetic patients with refractory macular oedema or patients with no adequate pre-operative view to administer laser treatment provide a challenge to the ophthalmologist. We wished to assess the use, safety and effect of intravitreal triamcinolone injection at the time of cataract surgery in patients with diabetic foveal oedema and sight limiting lens opacities. Method This was a longitudinal non-randomised prospective pilot study in 18 eyes (12 patients. All patients had visually significant lens opacities and either persistent diabetic foveal oedema unresponsive to laser treatment-group A, or foveal oedema with no adequate pre-operative view for laser treatment- group B. The cataract surgery was carried out under full aseptic technique using a self-sealing temporal incision and a foldable acrylic lens. Intravitreal triamcinolone was given infratemporally pars plana at the completion of the cataract surgery. The patients were reviewed at day 5, 2 weeks, 2 months and then every 3 months as required. The Wilcoxin matched-pairs test was used to assess the significance of the improvement in visual acuity at 2 months. Results Twelve patients with a total of 18 eyes were included in the study. There were 10 patients (15 eyes in group A and 3 patients (3 eyes in group B. Preoperatively 16 of the 18 eyes had a visual acuity of 6/24 or worse. Postoperatively 83% of patients had completely dry foveae at 2 weeks. Best-corrected visual acuities at two months review ranged from 6/6 to CF with 9 eyes (50% achieving 6/12 or better (7 eyes (47% in group A and 2 eyes (67% in group B. Three eyes had no recorded improvement in visual acuity, but no eyes had deterioration in acuity. The improvement in visual acuity was significant at p = 0.001. There were no significant sight threatening complications. Conclusion Intravitreal triamcinolone has been shown to lead to an improvement in macular oedema and visual improvement in

  11. Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

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    Zhou, Ai-Yi; Zhou, Chen-Jing; Yao, Jing; Quan, Yan-Long; Ren, Bai-Chao; Wang, Jian-Ming

    2016-01-01

    AIM To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria. METHODS The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated. RESULTS Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P<0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular

  12. Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

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    Isis A. S. Brito

    2015-01-01

    Full Text Available Radiation retinopathy (RR is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab. One must be aware of distant side effects after intravitreal injections.

  13. [A technique of rhesus monkey neural progenitor cells intravitreal transplant to rats].

    Science.gov (United States)

    Bian, Hui; Fan, Yao-Dong; Guo, Li-Yun; Yu, Hua-Lin

    2012-02-01

    To investigate a simple and effective intraocular xenotransplant technique of rhesus monkey neural progenitor cells to rats, mechanical injury was induced in the rat's right retina. And the GFP-labeled rhesus monkey neural progenitor cells suspension was slowly injected into the vitreous space of the right injured and left control eye. Confocal image suggested that the xenografted cells survived in both the injured and control eye, meanwhile the cells integrated in the injured right retina. The results demonstrated that intravitreal xenotransplant could be adopted as a simple and reliable method.

  14. Non-physician delivered intravitreal injection service is feasible and safe

    DEFF Research Database (Denmark)

    Rasul, Asrin; Subhi, Yousif; Sørensen, Torben Lykke

    2016-01-01

    retinopathy. We systematically reviewed the existing literature to provide an overview of the experiences in this transformational process. METHODS: We searched for literature on 22 September 2015 using PubMed, Embase, the Cochrane Library, CINAHL and the Web of Science. Eligible studies had to address any...... outcome based on non-physician delivered intravitreal therapy regardless of the study design. Being non-physician was defined as the injecting personnel not being a physician, but no further restrictions were made. RESULTS: Five studies were included with a total of 31,303 injections having been performed...

  15. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

    Science.gov (United States)

    Sánchez-Castro, Grimelda Yuriana; Hitos-Fájer, Alejandra; Mendoza-Schuster, Erick; Velez-Montoya, Raul; Velasco-Barona, Cecilio Francisco

    2008-01-01

    We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema. PMID:19668770

  16. Intravitreal bevacizumab therapy for idiophatic juxtafoveolar retinal telangiectasis associated with serous macular detachment

    Directory of Open Access Journals (Sweden)

    Paulo Escarião

    2014-01-01

    Full Text Available The authors describe a 50-year-old woman with group 2 juxtafoveolar retinal telangiectasis and macular detachment treated with a single-dose of intravitreous bevacizumab injection. There was an improvement in her visual acuity, with a decrease in retinal thickness showed by the optical coherence tomography and fluorescein leakage in the angiography on follow-up visits. No adverse events were observed as a result of the treatment used. After one year of follow-up, the vision remained stable and macular detachment did not recur.

  17. Hemiretinal vein occlusion with macular hemorrhage and edema treated with intravitreal bevacizumab

    Directory of Open Access Journals (Sweden)

    Yalamanchi S

    2011-10-01

    Full Text Available Shalini Yalamanchi, Harry W Flynn Jr.Department of Ophthalmology, Bascom Palmer Eye Institute, Miami Miller School of Medicine Miami, FL, USAAbstract: A 39-year-old male with decreased visual acuity and extensive macular hemorrhage and edema secondary to a hemiretinal vein occlusion was treated with multiple intravitreal injections of bevacizumab 1.25 mg every four to six weeks for over one year. Treatment outcomes were assessed by visual acuity and Cirrus spectral domain optical coherence tomography. Treatment resulted in ongoing visual and anatomic improvement, with resolution at the last visit.Keywords: retinal vein occlusion, macular edema, bevacizumab

  18. Subfoveal choroidal thickness changes after intravitreal bevacizumab therapy for neovascular age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Cihan; ünlü; Gurkan; Erdogan; Betul; Onal; Gunay; Betul; Ilkay; Sezgin; Akcay; Esra; Kardes

    2015-01-01

    <正>Dear Sir,Iam Dr.Cihanünlü,from the Department of Opthalmology,ümraniye Training and Research Hospital,Istanbul,Turkey.I write to present our study findings on subfoveal choroidal thickness(SFCT)changes after intravitreal bevacizumab(IVB)therapy for neovascular age-related macular degeneration(AMD).AMD is the leading cause of severe visual loss in adults older than 60y[1].Visual loss in late stages of AMD may be the result of one of the two processes:geographic atrophy(GA)or choroidal neovascularization(CNV).Many types of

  19. Peristence of triamcinolone crystals after intra-vitreal injection: Benign crystalline hyaloidopathy

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    Rafik Zarifa

    2013-01-01

    Full Text Available We report a case of unusually long persistence of triamcinolone crystals after intra-vitreal injection. Crystals were noted on fundus examination predominantly confined to the posterior pole. Optical coherence tomography localized the crystals to the posterior hyaloidal surface. Over 6 years of follow-up the patient has retained good visual acuity and no observable changes in the retina. As the condition clinically resembles both crystalline maculopathy and asteroid hyalosis, we suggest the term ′drug-induced benign crystalline hyaloidopathy′.

  20. [Foveolar effects of dexamethasone intravitreal implant in central retinal vein occlusion].

    Science.gov (United States)

    Bikbov, M M; Fayzrakhmanov, R R; Gil'manshin, T R; Gilyazova, I I

    2016-01-01

    To evaluate functional and morphometric parameters of the central retina in patients with postocclusive macular edema treated with dexamethasone intravitreal implant injection. We examined 5 patients (5 eyes) with newly diagnosed central retinal vein occlusion complicated by macular edema, including 4 men and 1 woman aged 55.8±3.65 years (experimental group). All the patients received a single injection of dexamethasone intravitreal implant. The maximum follow-up period was 12 months. The control group consisted of 5 presbiopic patients (10 eyes) aged 59.14±3.14 years. One month after injection, the best corrected visual acuity (BCVA) and central retinal light sensitivity improved (from 0.09±0.03 to 0.19±0.05 and from 3.18±0.19 to 11.07±0.97 dB, correspondingly), while foveolar thickness decreased from 425.36±57.87 to 273.75±36.65 µm. One year after the treatment, BCVA remained high and averaged 0.21±0.14. The total light sensitivity also remained higher than that at baseline, however, decreased down to 4.8±0.76 dB. Optical coherence tomography showed some flatness of the fovea. Foveolar thickness appeared 1.5 times higher than that in the control group and 1.2 times higher than that at the 1-month follow-up after dexamethasone intravitreal implant injection. Over the whole follow-up period, IOP has never significantly exceeded the baseline, optical media remained clear. 1. Dexamethasone intravitreal implant has been shown effective in resolving postocclusive macular edema, improving visual functions, and increasing central retinal light sensitivity within the first month after injection. 2. Positive changes in morphometric parameters of the central retina induced by the injection involve inner segments of photoreceptors as well as the outer nuclear, outer plexiform and inner nuclear layers. The morphofunctional effect persists for no less than 12 months after injection. 3. Over the 1-year follow-up period, there has been no negative influence of the

  1. EFFECTS OF REPEATEDLY HEADING A SOCCER BALL ON SERUM LEVELS OF TWO NEUROTROPHIC FACTORS OF BRAIN TISSUE, BDNF AND NGF, IN PROFESSIONAL SOCCER PLAYERS

    Directory of Open Access Journals (Sweden)

    B. Bamac

    2011-09-01

    Full Text Available The present study determined the effects of heading training on serum nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF levels in soccer players. Seventeen professional level male soccer players (mean ± SD, age 24 ± 4.4 years, were recruited from a 3rd league team. Each player completed 15 approved headings in about 20-25 minutes. Venous blood samples were obtained from soccer players before and after the heading training for analysis. Levels of NGF and BDNF in the serum were determined by a commercially available enzyme-linked immunosorbent assay (ELISA kit. Mean ± SD serum NGF levels were 18.71 ± 3.36 pg·ml-1 before training and 31.41 ± 7.89 pg·ml-1 after training (p=0.000. Mean ± SD serum BDNF levels were 22.32 ± 3.62 pg·ml-1 before training and 55.41 ± 12.59 pg·ml-1 after training (p=0.000. In this study heading a soccer ball was found to cause an increase in serum concentrations of NGF and BDNF. We suggest that the microtrauma caused by repetitive heading and/or the course of survival of the injured neurons may lead to increased NGF and BDNF levels.

  2. Testicular expression of NGF, TrkA and p75 during seasonal spermatogenesis of the wild ground squirrel (Citellus dauricus Brandt).

    Science.gov (United States)

    Zhang, H; Wang, Y; Zhang, J; Wang, L; Li, Q; Sheng, X; Han, Y; Yuan, Z; Weng, Q

    2015-08-10

    The nerve growth factor (NGF) not only has an essential effect on the nervous system, but also plays an important role in a variety of non-neuronal systems, such as the reproductive system. The aim of this study was to investigate the seasonal changes in expression of NGF and its receptors (TrkA and p75) in testes of the wild ground squirrel during the breeding and nonbreeding seasons. Immunolocalization for NGF was detected mainly in Leydig cells and Sertoli cells in testes of the breeding and nonbreeding seasons. The immunoreactivity of TrkA was highest in the elongated spermatids, whereas p75 in spermatogonia and spermatocytes in testes of the breeding season. In the nonbreeding season testes, TrkA showed positive immunostainings in Leydig cells, spermatogonia and primary spermatocytes, while p75 showed positive signals in spermatogonia and primary spermatocytes. Consistent with the immunohistochemical results, the mean mRNA and protein level of NGF and TrkA were higher in the testes of the breeding season, and then decreased to a relatively low level in the nonbreeding season. In addition, the concentration of plasma gonadotropins and testosterone were assayed by radioimmunoassay (RIA), and the results showed a significant seasonal change between the breeding and nonbreeding seasons. To conclude, these results of this study provide the first evidence on the potential involvement of NGF and its receptor, TrkA and p75 in the seasonal spermatogenesis and testicular function change of the wild ground squirrel.

  3. Relative abundance of tissue mRNA and association of the single nucleotide polymorphism of the goat NGF gene with prolificacy.

    Science.gov (United States)

    Naicy, Thomas; Venkatachalapathy, R Thirupathy; Aravindakshan, T V; Raghavan, K C; Mini, M; Shyama, K

    2016-10-01

    Nerve Growth Factor (NGF) promotes the development of pre-antral ovarian follicles through ovarian innervations and regulation of ovarian response to gonadotropins. The present study was conducted to study the tissue gene expression profile, to characterize the genetic variants, find associations of the NGF gene with prolificacy in the prolific Malabari and less prolific Attappady Black goats because NGF has an important role in reproduction by augmenting ovarian folliculogenesis. Relative abundance of NGF mRNA was greatest in reproductive tissues signifying its role in reproduction. The PCR-SSCP analysis of a 251bp fragment of Exon 3 of the NGF gene from the 277 goats revealed four diplotypes (EE, EF, FF and EG) with respective frequencies of 0.76, 0.22, 0.01 and 0.01. Sequencing of the representative samples revealed one synonymous and one novel non synonymous mutations (g.705G>A and g.715C>T). Statistical analysis indicated that the SNP g.705G>A was associated with litter size in Attappady Black goats (PNGF gene is a primary candidate gene affecting prolificacy in goats and may be used for Marker Assisted Selection (MAS) in goats, especially in lowly prolific Attappady Black goats.

  4. Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats.

    Science.gov (United States)

    Wisniewski, Miriam S W; Carvalho-Silva, Milena; Gomes, Lara M; Zapelini, Hugo G; Schuck, Patrícia F; Ferreira, Gustavo C; Scaini, Giselli; Streck, Emilio L

    2016-04-01

    Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-chain α-ketoacids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. However, the effect of accumulating α-ketoacids in MSUD on neurotrophic factors has not been investigated. Thus, the objective of the present study was to evaluate the effects of acute intracerebroventricular administration of α-ketoisocaproic acid (KIC) on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brains of young male rats. Ours results showed that intracerebroventricular administration of KIC decreased BDNF levels in hippocampus, striatum and cerebral cortex, without induce a detectable change in pro-BDNF levels. Moreover, NGF levels in the hippocampus were reduced after intracerebroventricular administration of KIC. In conclusion, these data suggest that the effects of KIC on demyelination and memory processes may be mediated by reduced trophic support of BDNF and NGF. Moreover, lower levels of BDNF and NGF are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying the psychopathology of MSUD, supporting the hypothesis of a neurodegenerative process in MSUD.

  5. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer's disease rat model.

    Science.gov (United States)

    Marei, Hany E S; Farag, Amany; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Lashen, Samah; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-01-01

    In this study, we aim to demonstrate the fate of allogenic adult human olfactory bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into different neuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotection following their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, genetically engineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted into the hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post transplantation revealed a 1.89 fold increase with respect to the initial cell population, indicating a marked ability for survival and proliferation. In addition, 54.71 ± 11.38%, 30.18 ± 6.00%, and 15.09 ± 5.38% of engrafted OBNSCs were identified by morphological criteria suggestive of mature neurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably be attributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF. © 2014 Wiley Periodicals, Inc.

  6. Correlations between amygdala volumes and serum levels of BDNF and NGF as a neurobiological markerin adolescents with bipolar disorder.

    Science.gov (United States)

    Inal-Emiroglu, F Neslihan; Karabay, Nuri; Resmi, Halil; Guleryuz, Handan; Baykara, Burak; Alsen, Sevay; Senturk-Pilan, Birsen; Akay, Aynur; Kose, Samet

    2015-08-15

    The amygdala is repeatedly implicated as a critical component of the neurocircuitry regulating emotional valence. Studies have frequently reported reduced amygdala volumes in children and adolescents with bipolar disorder (BD). Brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play critical roles in growth, differentiation, maintenance, and synaptic plasticity of neuronal systems in adolescent brain development. The aim of the present study was to assess amygdala volumesand its correlation with serum levels of NGF and BDNF in euthymic adolescents with BD and healthy controls. Using structural MRI, we compared the amygdala volumes of 30 euthymic subjects with BD with 23 healthy control subjects aged between 13 and 19 years during a naturalistic clinical follow-up. The boundaries of the amygdala were outlined manually. Serum BDNF and NGF levels were measured using sandwich-ELISA and compared between the study groups. The right or left amygdala volume did not differ between the study groups.The right and left amygdala volumes were highly correlated with levels of BDNF in the combined BD group and the valproate-treated group.Both R and L amygdala volumes were correlated with BDNF levels in healthy controls. The left amygdala volumes were correlated with BDNF levels in the lithium-treated group. This cross-sectional study cannot inform longitudinal changes in brain structure. Further studies with larger sample sizes are needed to improve reliability. The correlations between amygdala volumes and BDNF levels might be an early neuromarker for diagnosis and/or treatment response in adolescents with BD. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure.

    Science.gov (United States)

    Suzukawa, J; Omori, K; Okugawa, G; Fujiseki, Y; Heizmann, C W; Inagaki, C

    1999-07-10

    A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.

  8. Choroidal neovascularization in pathologic myopia: intravitreal ranibizumab versus bevacizumab--a randomized controlled trial.

    Science.gov (United States)

    Gharbiya, Magda; Giustolisi, Rosalia; Allievi, Francesca; Fantozzi, Nicoletta; Mazzeo, Luigi; Scavella, Vittorio; Gabrieli, Corrado Balacco

    2010-03-01

    To compare the short-term efficacy and safety of intravitreal ranibizumab versus bevacizumab in treating myopic choroidal neovascularization (CNV). Prospective, comparative, randomized, interventional study. Thirty-two eyes from 32 patients with myopic CNV were consecutively enrolled and randomly treated, in a 1:1 ratio, with intravitreal ranibizumab (0.5 mg) or bevacizumab (1.25 mg) as needed, after the first injection. ETDRS best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 6 months. No statistically significant difference in the BCVA improvement, as well as in the FCT reduction, was found between groups during follow-up (P value at 1, 3, 6 months > .05). Complete resolution of fluorescein leakage was observed in all 16 bevacizumab-treated eyes and in 15 out of 16 (93.7%) ranibizumab-treated eyes. No ocular or systemic adverse effects from treatment were encountered. This randomized clinical study cannot determine a statistically significant difference in anti-VEGF treatment effect between ranibizumab and bevacizumab for the treatment of CNV secondary to pathologic myopia. A larger study is required to determine the relative efficacy and duration of action of these drugs. (c) 2010 Elsevier Inc. All rights reserved.

  9. Characteristic analysis on susceptibility weighted imaging of intravitreous foreign body of autologous eyelashes in rabbits

    Institute of Scientific and Technical Information of China (English)

    YANG Yun-jun; CHENG Jing-liang; WANG Juan; ZHANG Yong; LI Hua-li

    2010-01-01

    Objective: To explore the characteristics of susceptibility weighted imaging (SWI) of the intravitreous foreign body of autologous eyelashes in rabbits.Methods: A total of 12 New Zealand white rabbits,either sex, weighing 2.5-3.5 kg, and provided by the Experimental Animal Center of Henan Province were employed in this study. For each rabbit, 5 autologous eyelashes (1 cm in length and 0.2-0.3 mm in diameter) were implanted into the right ocular vitreum, while the left control ocular vitreum received sham operation but nothing was implanted. SWI sequential test was made 2 hours postoperatively. Then the rabbits were killed and the specimens of the vitreous bodies of the rabbits were obtained. Hematoxylin and eosin staining and histological examinations were performed. Results: The autologous eyelashes in 8 ocular vitreums of rabbits showed linear low signal intensity on the magnitude images and susceptibility weighted images, but linear high signal intensity on the phase images. Among the 12experimental rabbits, 5 eyelashes in the right vitreum were completely shown in 3 rabbits, partly shown in 5 rabbits (2eyelashes shown in 3 rabbits and 3 eyelashes shown in 2rabbits), and not shown in 4 rabbits. Conclusions: SWI of the foreign body ofintravitreous autologous eyelashes in rabbits has its own characteristics. The combined application of SWI sequential magnitude images, susceptibility weighted images and phase images is helpful to the detection and diagnosis of intravitreous autologous eyelashes in rabbits.

  10. [Time course of changes in aqueous flare following intravitreous gas injection in rabbits].

    Science.gov (United States)

    Yamamoto, K

    1991-06-01

    The quantitative changes of the aqueous flare following intravitreous gas injection were determined by laser flare-cell metry in rabbits. A volume of 0.4 ml of air, 100% sulfur hexafluoride (SF6), or 100% perfluoropropane (C3F8), was injected separately into the vitreous of pigmented rabbits. The normal range of the aqueous flare was 7.8 +/- 3.0 (photon counts/msec). Each model showed an increase of aqueous flare on the first day (air: 18.9 +/- 9.1, SF6: 19.5 +/- 11.5, C3F8: 40.8 +/- 22.8). Subsequently, the aqueous flare of air-injected eyes gradually decreased, while that of SF6-injected eyes increased on the 4th day, and then gradually decreased. Also that of C3F8-injected eyes increased on the 4th day, and the 7th day, then decreased on the 14th day, but it was still higher than normal. Cataracts developed in two of the five eyes injected with SF6 and all of the four eyes injected with C3F8. These findings revealed that following intravitreous gas injection, disruption of the blood-ocular barrier depended on the expansibility of the gas and the length of time it remained in the vitreous cavity.

  11. Apoptosis and electroretinogram after intravitreal injection of methotrexate in an experimental rabbit model.

    Science.gov (United States)

    Aly, Eman; Ebrahim, Amal

    2016-04-01

    The aim of this study was to explore the changes in electroretinogram of rabbit retina and apoptosis in methotrexate-induced toxicity. Rabbits were divided into 5 groups. Group I served as control in which saline solutions was injected intravitreally. Methotrexate (800 μg, 1.76 μmol) was injected into the vitreous of both eyes of rabbits groups II, III, IV and V by an insulin injector with a 26 gauge needle under general anesthesia. Retinal function was assessed by electroretinogram (ERG) after 2, 4, 10 days and one month then animals were decapitated. The eyes were enucleated and processed for DNA fragmentation studies by gel electrophoresis to retinae and measurement of caspase-3 activities. The results indicated a significant reduction (p ˂ 0.05) in a- and b-wave, a time-dependent appearance of the typical ladder pattern of internucleosomal fragmentation, a characteristic of apoptosis and increase of relative caspase-3 activity after methotrexate intravitreal injection. Methotrexate lead to apoptosis, increase of caspase-3 and affect retinal function.

  12. Use of intravitreal injection of triamcinolone acetonide in the treatment of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Gopal Lekha

    2007-01-01

    Full Text Available Age-related macular degeneration (AMD is now considered an important and leading cause of blindness among elderly patients in developed and developing countries. AMD has two forms, dry and wet; both can lead to visual loss. However, occurrence of subfoveal choroidal neovascular (CNV membrane in the wet form results in severe visual impairment. Treatment options for choroidal neovascularization are available in order to maintain and in some cases improve vision. Photodynamic therapy (PDT has been used to treat both classic and occult membranes. It has known to cause choroidal hypoperfusion and production of vascular endothelial growth factor. Intravitreal steroid can possibly reduce the damage caused due to these undesirable effects. In the recent past, intravitreal injection of triamcinolone acetonide (IVTA has been used extensively as an adjunct to PDT in AMD in order to reduce the number of PDT sessions and evaluate possible beneficial effects on vision. This article reviews the pharmacological attributes of triamcinolone, available evidence of its use as monotherapy or combination therapy to treat AMD, ocular side-effects thereof and ongoing clinical trials on IVTA.

  13. Intravitreal Triamcinolone Acetonide for Macular Edema in HLA-B27 Negative Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    M.M. Moschos

    2010-12-01

    Full Text Available We report a case of a human leukocyte antigen B27 (HLA-B27-negative patient with cystoid macular edema (CME and ankylosing spondylitis (AS after treatment with triamcinolone acetonide. The patient complained of deterioration of visual acuity of the right eye during the last 10 days. At presentation visual acuity of the right eye was 0.2, and the ophthalmic examination did not reveal any sign of active uveitis. Fluorescein angiography (FA and ocular coherent tomography (OCT showed CME. The left eye was normal with a visual acuity of 0.9. Eight weeks after intravitreal injection of triamcinolone acetonide, visual acuity improved to 0.8 and OCT revealed regression of macular edema. Six months later no recurrence was observed. Our case report indicates for the first time that CME may occur in AS independently of the presence of HLA-B27 and intraocular inflammation. Intravitreal use of triamcinolone acetonide can reduce macular edema and restore visual acuity.

  14. Evaluation of vitreoretinal interface changes in patients receiving intravitreal anti-VEGF therapy.

    Science.gov (United States)

    Kinra, Vartika; Singh, Satvir; Khanduja, Sumeet; Nada, Manisha

    2017-03-15

    To study the effects of repeated intravitreal injection of anti-VEGF drug bevacizumab on the vitreoretinal interface (VRI). Patients undergoing intravitreal injection of bevacizumab were enrolled. Eyes with media haze, uveitis, high myopia, history of cataract surgery or laser capsulotomy in last 6 months and complicated pseudophakia were excluded. VRI evaluation was done monthly for a minimum of 6 months. The nature and timing of the change(s) event was recorded. A total of 100 eyes were evaluated. Thirty-seven eyes developed new vitreoretinal interface change event (VICE). Pseudophakia (OR = 5.23, 95% CI = 1.99-14.07, p = 0.001), pre-injection VRI abnormality (OR = 2.63, 95% CI = 1.13-6.14, p = 0.024) and older age at enrollment (62.6 ± 13.9 vs. 56.3 ± 14 years) were risk factors for development of VICE. Eighty percent of interface events occurred in the first 3 months of therapy. Eight needed surgical intervention for consequences of vitreoretinal separation. VICE is not infrequent in eyes receiving anti-VEGF therapy though rarely need surgical intervention. The first 3 months are the critical months to watch out for these events. The treating ophthalmologists must keep the risk factors for development of in mind and monitor and counsel patients accordingly.

  15. DEPLOYMENT OF SIX SIGMA METHODOLOGY TO REDUCE COMPLICATIONS IN INTRAVITREAL INJECTIONS

    Directory of Open Access Journals (Sweden)

    İbrahim SAHBAZ

    2014-04-01

    Full Text Available The purpose of this study is to show how a private eye care center in Turkey initiated Six Sigma principles to reduce the number of complications encountered during and after intravitreal injections. Data were collected for 30-months. To analyse the complications among 229 injections administered on 106 patients, main tools of Six Sigma’s Define-Measure-Analyze-Improve-Control (DMAIC improvement cycle such as SIPOC table, Fishbone Diagram and, Failure, Mode and Effect Analysis were implemented. Sources and root causes of seven types of complications were identified and reported. For a successful intravitreal injection, experience of the retina specialist, attention of the retina specialist and patient’s ocular pathology were determined to be the “critical few” factors whereas, sterilization and hygiene, dosage of drug/agent and chemical properties of drug/agent were found to be the “trivial many”factors. The most frequently occuring and the complication with the highest hazard score was found to be subconjunctival haemorrhage. The process sigma level of the process was measured to be 3.2657. The surgical team concluded that six of the complications (out of seven should be significantly reduced by taking the necessary preventative measures.

  16. SAFETY OF INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX): The SAFODEX study. Incidence and Risk Factors of Ocular Hypertension.

    Science.gov (United States)

    Malclès, Ariane; Dot, Corinne; Voirin, Nicolas; Vié, Anne-Laure; Agard, Émilie; Bellocq, David; Denis, Philippe; Kodjikian, Laurent

    2017-07-01

    To analyze the incidence, risk factors, and time course of intraocular pressure elevation after intravitreal dexamethasone implant (Ozurdex). The medical charts of 421 consecutive eyes (361 patients) receiving one or more Ozurdex implant between October 2010 and February 2015 were reviewed retrospectively. Ocular hypertension was defined as intraocular pressure of at least 25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were retinal vein occlusion (34%), diabetic macular edema (30%), postsurgical macular edema (17%), uveitis (14%), and other etiologies (5%). Among 1,000 intravitreal injections, ocular hypertension was recorded for 28.5% of injected eyes over a mean follow-up period of 16.8 months (3-55). Intraocular pressure-lowering medication was required for 31% of eyes. Only three eyes with preexisting glaucoma required filtering surgery to manage postinjection intraocular pressure elevation. Early retreatment between the third and fourth month does not increase the risk of intraocular pressure elevation. Younger age, male sex, Type 1 diabetes, preexisting glaucoma treated with dual or triple therapy, and a history of retinal vein occlusion or uveitis were significant risk factors for ocular hypertension after dexamethasone implant injection (P hypertension after Ozurdex implant were generally transient and successfully managed with topical treatment. An analysis of the risk factors may help to determine the risk-benefit ratio for individual patients treated with dexamethasone implants.

  17. Bilateral Hypertensive Retinopathy Complicated with Retinal Neovascularization: Panretinal Photocoagulation or Intravitreal Anti-VEGF Treatment

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    Odysseas Georgiadis

    2014-07-01

    Full Text Available Purpose: To present the case of a patient with bilateral hypertensive retinopathy complicated with retinal neovascularization who received anti-VEGF intravitreal injection in one eye and panretinal photocoagulation (PRP in the fellow eye. Methods: A 33-year-old male patient presented with gradual visual loss in both eyes for the last 5 months. At that time, he was examined by an ophthalmologist and occlusive retinopathy due to malignant systematic hypertension was diagnosed. He was put on antihypertensive treatment but no ophthalmic treatment was undertaken. At presentation, 5 months later, best-corrected visual acuity (BCVA was 0.1 in the right eye (RE and 0.9 in the left eye (LE. Fundus examination was compatible with hypertensive retinopathy complicated with retinal neovascularization. Fluorescein angiography (FFA revealed macular ischemia mainly in the RE and large areas of peripheral retinal ischemia and neovascularization with vascular leakage in both eyes. The patient was treated with two anti-VEGF (ranibizumab injections with 2 months interval in the RE and PRP laser in the LE. Results: Follow-up examination after 12 months showed mild improvement in BCVA, and FFA documented regression of retinal neovascularization in both eyes. Conclusion: Hypertensive retinopathy can be rarely complicated with retinal neovascularization. Treatment with PRP can be undertaken. In our case, the use of an intravitreal anti-VEGF agent seemed to halt its progression satisfactorily.

  18. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma.

    Science.gov (United States)

    Mansour, Ahmad M; Arevalo, J Fernando; Al Kahtani, Eman; Zegarra, Hernando; Abboud, Emad; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J; Pulido, Jose S; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S; Gentile, Ronald C; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y Y; Massoud, Vicky; Ghazi, Nicola G

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  19. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

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    Grimelda Yuriana Sánchez-Castro

    2008-10-01

    Full Text Available Grimelda Yuriana Sánchez-Castro1, Alejandra Hitos-Fájer1, Erick Mendoza-Schuster1, Raul Velez-Montoya2, Cecilio Francisco Velasco-Barona11Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Anterior Segment; 2Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Retina departmentAbstract: We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema.Keywords: posterior capsule opacification, posterior capsule neovascularization, cataract surgery, postoperative complications, intravitreal bevacizumab

  20. Retinal toxicity of intravitreally injected plain and liposome formulation of fluconazole in rabbit eye

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    Velpandian Thirumurthy

    2006-01-01

    Full Text Available Purpose: Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. Fluconazole has been effective against Candida albicans in various animal models. Our objective was to evaluate retinal toxicity of plain and liposome formulation of fluconazole at various dose levels after intravitreal injection. Materials and Methods: Twelve New Zealand albino rabbits weighing 2-2.5 kg were used. Two rabbits were used for every dose level. Liposome formulation containing 100 and 200 µg of fluconazole in sterile phosphate buffer solution and plain fluconazole at concentrations of 100, 200, 400 and 800 µg in 0.1 ml of sterile normal saline were injected intravitreally into the right eyes. The left eyes received 0.1 ml normal saline or 0.1 ml of liposome formulation without fluconazole. One week later, the animals were sacrificed, their eyes enucleated and processed for light microscopy and scanning electron microscopy. Results: It showed that plain fluconazole at a concentration of 100 µg and above caused retinal changes, with disorganization of the photoreceptor outer segments. However, liposome formulation of fluconazole (200 µg/0.1 ml did not show any significant microscopic changes of the retina. Conclusion: The liposome formulation decreased the retinal toxicity of fluconazole up to the studied concentration of 200 µg/0.1 ml.

  1. Comparison of intravitreal ranibizumab and bevacizumab treatment for retinopathy of prematurity

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    Muhammet Kazim Erol

    2015-12-01

    Full Text Available ABSTRACT Purpose: To compare the efficacy of intravitreal ranibizumab and bevacizumab treatment for type 1 retinopathy of prematurity (ROP. Methods: 36 eyes of 20 patients with type 1 ROP who received anti-vascular endothelial growth factor (anti-VEGF intravitreal injections between August 2011 and February 2013 were retrospectively evaluated. Fifteen eyes of 8 patients received 0.25 mg ranibizumab (group 1, and 21 eyes of 12 patients received 0.625 mg bevacizumab (group 2. Eyes were examined by indirect ophthalmoscopy on the first day, third day, first week, and first month and as required after injections. Laser photocoagulation was performed in cases with progression of ROP. Results: The mean gestation time was 26.2 ± 2.7 weeks in group 1 patients and 27.1 ± 2.5 weeks in group 2 patients. No statistical difference in the time of gestation was observed between the two groups. The mean follow-up period was 20 ± 4.5 months. Laser photocoagulation was performed in 6 of 15 eyes from group 1 and 2 of 21 eyes from group 2. No eyes developed retinal detachment during the follow-up period. Conclusion: Ranibizumab and bevacizumab showed an efficacy in the treatment of type 1 ROP. The incidence of disease relapse was higher in eyes which received ranibizumab. Further randomized, controlled clinical trials are required to compare the efficacy of ranibizumab and bevacizumab.

  2. Intravitreal bevacizumab injections for diabetic macular edema – predictors of response: a retrospective study

    Science.gov (United States)

    Joshi, Lavnish; Bar, Asaf; Tomkins-Netzer, Oren; Yaganti, Satish; Morarji, Jiten; Vouzounis, Panayiotis; Seguin-Greenstein, Sophie; Taylor, Simon R; Lightman, Sue

    2016-01-01

    Background Outcomes of intravitreal antivascular endothelial growth factor injections are variable among patients with diabetic macular edema (DME). The aim of this study was to determine the ocular and systemic predictors of DME response to intravitreal bevacizumab (IVB). Methods Retrospective review over 2 years of 78 eyes from 54 patients. An anatomical response to IVB was defined as a 20% reduction in central macula thickness after the first course (three injections) of IVB. Results Twenty-eight percent of patients had an anatomical response after the first course of IVB. Systemic hypertension (odds ratio, 95% confidence interval: 12.1, 0.7–21) was a statistically significant predictor (P=0.025) of a good response to IVB, whereas previous macular laser was a statistically significant (P=0.0005) predictor of a poor response (0.07, 0.01–0.32). Sixty-eight percent of eyes underwent subsequent treatment for DME after the first course of IVB. The visual acuity gain at 24 months in hypertensive (0.7±3.6 letters) and nonhypertensive (5.2±3.7 letters) patients was not significantly different (P=0.41). Conclusion Hypertension and previous macular laser were positive and negative predictors of response to IVB, respectively. However, long-term visual acuity changes were not significantly different between eyes with and without systemic hypertension. PMID:27799737

  3. The Use of Intravitreal Ranibizumab for Choroidal Neovascularization Associated with Vogt-Koyanagi-Harada Syndrome

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    A. M. Kolomeyer

    2011-01-01

    Full Text Available Purpose. To describe the use of intravitreal ranibizumab for choroidal neovascular membrane (CNVM secondary to Vogt-Koyanagi-Harada (VKH syndrome. Methods. Interventional case report. Results. A 50-year-old woman presented with conjunctival injection and bilateral eye pain. Vision was 20/400 and 20/80 in the right and left eyes, respectively. Bilateral iritis, vitritis, and choroidal thickening were evident. Exudative retinal detachment was present in the left eye. Corticosteroid treatment improved vision to 20/40 bilaterally. Methotrexate (MTX was initiated and vision remained stable for 3 months. After a 5-month loss to follow-up, vision in the left eye decreased to finger counting (CF and a parafoveal CNVM was identified. After 3 intravitreal ranibizumab injections, vision improved to 20/40. Twelve months later, despite inflammation control, vision decrease to CF due to recurrent CNVM. A fourth ranibizumab injection was given. Twenty months later, best-corrected vision was 20/400, and an inactive CNVM was present in the left eye. Conclusion. After initial CNVM regression and visual acuity improvement due to ranibizumab, the CNVM recurred and became refractory to treatment. Despite control of inflammation and neovascularization, VKH chronicity lead to permanent vision loss in our patient. A combinational treatment approach may be required in such patients.

  4. Intravitreal Injection of Dexamethasone Implant in Serous Macular Detachment Associated with Waldenström's Disease

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    Vito Fenicia

    2013-07-01

    Full Text Available Purpose: To evaluate the efficacy of one intravitreal injection of dexamethasone (Ozurdex®; Allergan, Inc., Irvine, Calif., USA in serous macular detachment (SMD of one eye, associated with bilateral central retinal vein occlusion (CRVO in a patient affected by Waldenström's macroglobulinemia (WM. Patients and Methods: A female patient, affected by WM, complained of a progressive decrease in visual acuity, mainly in the left eye (LE. SMD in the LE associated with bilateral CRVO was diagnosed. One intravitreal injection of dexamethasone was administered in the LE and the patient was tested 1, 2, and 6 months after the injection. Results: 1, 2, and 6 months after the injection, the spectral domain optical coherence tomography (SD-OCT showed a progressive slight reduction of foveal thickness that was not related to any improvement of visual function. Conclusions: Treatment with dexamethasone (Ozurdex induced a progressive slight reduction of SMD but no improvement of visual acuity, and it is possible that this is related to the condition of hematic hyperviscosity that is present in WM.

  5. Choroidal osteoma with choroidal neovascular membrane: Successful treatment with intravitreal bevacizumab

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    Neeraj Pandey

    2010-09-01

    Full Text Available Neeraj Pandey, Ayachit GuruprasadMM Joshi Eye Institute, Hubli, Karnataka, IndiaAbstract: An otherwise healthy 27-year-old woman presented with complaints of sudden painless blurred vision in the right eye for one week. On examination, visual acuity was 20/30 in the right eye and 20/20 in left eye. Fundus examination OS was normal, but OD demonstrated an elevated, opaque, yellowish parapapillary choroidal lesion with grayish membrane associated with minimal subretinal fluid, suggestive of a choroidal neovascular membrane in the center. B-scan ultrasonography revealed findings consistent with a choroidal osteoma. Fundus fluorescein angiography of the right eye revealed a relatively well defined area of hyperfluorescence that increased in size and intensity in the later phases, suggestive of active extrafoveal choroidal neovascular membrane. Optical coherence tomography confirmed the extrafoveal choroidal neovascular membrane with subfoveal fluid. She was treated with intravitreal bevacizumab OD. At the two-week visit, vision OD improved to 20/20. Fluorescein angiography and optical coherence tomography revealed a resolved choroidal neovascular membrane. Intravitreal bevacizumab may be an effective alternative in the management of choroidal neovascular membrane secondary to choroidal osteoma.Keywords: osteoma, choroidal neovascular membrane, optical coherence tomography, bevacizumab

  6. Incidence of acute endophthalmitis after intravitreal bevacizumab injection in a single clinical center.

    Science.gov (United States)

    Falavarjani, Khalil Ghasemi; Modarres, Mehdi; Hashemi, Masih; Parvaresh, Mohammad M; Naseripour, Masood; Zare-Moghaddam, Abbas; Nekoozadeh, Shahbaz

    2013-05-01

    To assess the rate of infectious endophthalmitis in a single clinical center in Iran and to compare the rate of endophthalmitis in patients receiving postinjection antibiotics with those who did not. A retrospective chart review of patients who received intravitreal injections of bevacizumab was undertaken. Cases of clinical diagnoses of endophthalmitis were reviewed. Bevacizumab was obtained at the time of injection from a commercially available vial after aseptic cleansing of the rubber cover. Five patients (six eyes) developed clinical endophthalmitis after the intravitreal bevacizumab injection. The risk per injection was 0.10% (6/5,901). One culture-positive case was found overall. Postinjection antibiotic drops were prescribed for 68% of eyes. All endophthalmitis cases were among those who received postoperative antibiotic eye drops. The difference in the rates of endophthalmitis between those receiving postinjection antibiotics and those who did not was not statistically significant (P = 0.18). A low risk of endophthalmitis consistent with the range of previous studies was observed notwithstanding the usage of multiple use of a single vial. Postinjection antibiotic drops may not be necessary.

  7. Preliminary study of Conbercept injected intravitreally for the treatment of wet age-related macular degeneration

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    Ying Qin

    2017-08-01

    Full Text Available AIM:To observe the preliminary efficacy of conbercept injected intravitreally for the treatment of wet age-related macular degeneration(wAMD.METHODS:Seventeen wAMD patients(18 eyeswere selected to receive conbercept injection. All patients were given a single conbercept injection every month, 3 times. Before and after 1, 2, 3mo of the injection, the best corrected visual acuity(BCVA, intraocular pressure(IOP, measured by Non-contact tonometer, fundus photography, fundus fluorescein angiography(FFA, indocyanine green angiography(ICG, optical coherence tomography(OCTexamination and the complications incidence were compared.RESULTS:Three months after conbercept injection, the BCVA improved in 15 eyes(83%, stable in 3 eyes(17%. Before treatment, the average central macular thickness was 421.72±54.43μm, at 1 and 2 and 3mo after treatment, the average central macular thickness was 337.89±25.88μm, 293.56±26.87μm, 266.89±19.10μm respectively. There were significant differences compared with before and after injection(PCONCLUSION:Intravitreal injection conbercept for wAMD can significantly improve the visual function, reduce the macular edema and the leakage with higher safety and less complications. However the prolonged efficacy needs further observation.

  8. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

    Science.gov (United States)

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A.; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J.; Pulido, Jose S.; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S.; Gentile, Ronald C.; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y. Y.; Massoud, Vicky; Ghazi, Nicola G.

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. PMID:25147732

  9. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

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    Ahmad M. Mansour

    2014-01-01

    Full Text Available We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF inhibitor for choroidal new vessel (CNV formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n=15; P=0.001, 105.3 microns at 1 year (n=10; P=0.03, and 157.6 microns at 2 years (n=7; P=0.08. BCVA improved by 3.3 lines at 6 months after therapy (n=26; P<0.001, 2.8 lines (n=20; P=0.01 at 1 year, and 3.1 lines (n=13; P=0.049 at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  10. Cytokine Kinetics after Monthly Intravitreal Bevacizumab for Retinal Vein Occlusion Associated with Macular Oedema.

    Science.gov (United States)

    Noma, Hidetaka; Mimura, Tatsuya; Yasuda, Kanako; Shimura, Masahiko

    2016-01-01

    To investigate changes of cytokines after intravitreal anti-vascular endothelial growth factor (VEGF) therapy in patients with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Monthly doses of intravitreal bevacizumab (IVB) were administered for 6 months to treat macular oedema associated with BRVO or CRVO. Aqueous humour levels of 11 factors were measured using samples obtained from 24 patients during IVB treatment (16 BRVO patients and 8 CRVO patients). Levels of VEGF, placental growth factor (PlGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, IL-12 (p70), and IL-13 were measured by suspension array. Vision and macular oedema improved significantly after monthly IVB. Furthermore, there was a significant decrease in sVEGFR-1, VEGF, PDGF-AA, MCP-1, and IL-8 after monthly IVB. On the other hand, there were no significant changes of sVEGFR-2, PlGF, sICAM-1, or IL-6 after monthly IVB. After 1 dose of bevacizumab, changes of VEGF, visual acuity, and optical coherence tomography parameters almost occurred in parallel. These findings suggest an important role of the cytokine network in both BRVO and CRVO, and may contribute to a new strategy for macular oedema associated with retinal vein occlusion. © 2016 S. Karger AG, Basel.

  11. The effect of intravitreal bevacizumab and ranibizumab on cutaneous tensile strength during wound healing

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    Christoforidis JB

    2013-01-01

    Full Text Available John B Christoforidis,1 Jillian Wang,2 Angela Jiang,2 James Willard,5 Cedric Pratt,2 Mahmoud Abdel-Rasoul,3 Sashwati Roy,4 Heather Powell51Department of Ophthalmology and Vision Science, College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Ophthalmology, College of Medicine, The Ohio State University, Columbus, OH, USA; 3Center for Biostatistics, The Ohio State University, Columbus, OH, USA; 4Center Surgery, The Ohio State University, Columbus, OH, USA; 5Department of Materials Science, College of Engineering, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension and by histopathology during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls 1 and 2 weeks following intravitreal injection.Methods: A total of 120 New Zealand white rabbits were randomly assigned to one of three treatment groups each consisting of 40 rabbits. Each group received intravitreal injections of bevacizumab, ranibizumab, or normal saline. Immediately afterwards, each rabbit underwent four 6 mm full-thickness dermatologic punch biopsies. Twenty rabbits from each agent group underwent wound harvesting on day 7 or day 14. The skin samples were stained for CD34 for vascular endothelial cells on day 7, and maximal wound tensile load was measured on days 7 and 14. Quantitative assessment of mean neovascularization (MNV scores was obtained from 10 contiguous biopsy margin 400× fields of CD34-stained sections by two independent observers.Results: Wound tension reading means (N with standard error and adjusted P-values on day 7 were: saline placebos, 7.46 ± 0.87; bevacizumab, 4.50 ± 0.88 (P = 0.041; and ranibizumab, 4.67 ± 0.84 (P = 0.025. On day 14 these were: saline placebos, 7.34 ± 0.55; bevacizumab, 6.05 ± 0.54 (P = 0.18; and ranibizumab 7.99 ± 0.54 (P = 0.40. MNV scores in CD34 stained sections were

  12. Treatment of Retinitis Pigmentosa-Associated Cystoid Macular Oedema Using Intravitreal Aflibercept (Eylea despite Minimal Response to Ranibizumab (Lucentis: A Case Report

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    Stacey A. Strong

    2016-09-01

    Full Text Available Background: We present an interesting case of bilateral retinitis pigmentosa (RP-associated cystoid macular oedema that responded on two separate occasions to intravitreal injections of aflibercept, despite previously demonstrating only minimal response to intravitreal ranibizumab. This unique case would support a trial of intravitreal aflibercept for the treatment of RP-associated cystoid macular oedema. Case Presentation: A 38-year-old man from Dubai, United Arab Emirates, presented to the UK with a 3-year history of bilateral RP-associated cystoid macular oedema. Previous treatment with topical dorzolamide, oral acetazolamide, and intravitreal ranibizumab had demonstrated only minimal reduction of cystoid macular oedema. Following re-confirmation of the diagnosis by clinical examination and optical coherence tomography imaging, bilateral loading doses of intravitreal aflibercept were given. Central macular thickness reduced and the patient returned to Dubai. After 6 months, the patient was treated with intravitreal ranibizumab due to re-accumulation of fluid and the unavailability of aflibercept in Dubai. Only minimal reduction of central macular thickness was observed. Once available in Dubai, intravitreal aflibercept was administered bilaterally with further reduction of central macular thickness observed. Visual acuity remained stable throughout. Conclusions: This is the first case report to demonstrate a reduction of RP-associated CMO following intravitreal aflibercept, despite inadequate response to ranibizumab on two separate occasions. Aflibercept may provide superior action to other anti-VEGF medications due to its intermediate size (115 kDa and higher binding affinity. This is worthy of further investigation in a large prospective cohort over an extended time to determine the safety and efficacy of intravitreal aflibercept for use in this condition.

  13. Assessment of the effect of intravitreal triamcinolone acetonide on the chorioretinal and vitreous inflammatory reaction to cryotherapy in rabbits

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    Eugênio Santana de Figueirêdo

    2012-10-01

    Full Text Available PURPOSE: To evaluate the inflammatory response in the choroid, retina and vitreous in rabbit eyes underwent cryotherapy followed by intravitreal triamcinolone acetonide and to compare with those underwent cryotherapy followed by intravitreal injection of saline solution. METHODS: This is a prospective case-control study. Surgical procedures were performed in eleven rabbits. Two animals were excluded because they did not complete the postoperative period or had intraoperative or postoperative complications. All rabbits underwent superior temporal peritomy and transscleralcryotherapy in both eyes. After cryotherapy, animals received intravitreal injection of triamcinolone acetonide in one eye and saline solution in the fellow eye. Animals were sacrificed seven days after the procedure and their eyes were enucleated. Histological sections of eyeballs were prepared and the vitreous humor was aspirated. The count of inflammatory cells was performed by light microscopy. RESULTS: Histological sections of both eyes of nine rabbits were analyzed. Inflammatory cells were found only in the choroid. There was no statistically significant difference in the number of inflammatory cells between the two groups, regardless of cell type analyzed. CONCLUSION: This study showed no statistically significant difference between the use or absence of intravitreal triamcinolone acetonide in the inflammatory response to cryotherapy in rabbit eyes. Studies with larger samples are needed to confirm the trend of this paper.

  14. Photodynamic monotherapy or combination treatment with intravitreal triamcinolone acetonide, bevacizumab or ranibizumab for choroidal neovascularization associated with pathological myopia

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    Pukhraj Rishi

    2011-01-01

    Full Text Available This retrospective, interventional case series analyses treatment outcomes in eyes with choroidal neovascularization (CNV secondary to pathological myopia, managed with photodynamic therapy, (PDT, (Group 1, N = 11, PDT and intravitreal triamcinolone acetonide (4 mg/0.1ml (Group 2, N = 3, PDT and intravitreal anti-vascular endothelial growth factor (anti-VEGF bevacizumab 1.25 mg/0.05 ml, ranibizumab 0.5 mg/0.05 ml and reduced-fluence PDT and intravitreal ranibizumab 0.5 mg/0.05 ml (Group 3, N=12. All the patients underwent PDT. Intravitreal injections were repeated as required. SPSS 14 software was used to evaluate the data. Wilcoxon signed ranks test was used to evaluate pre- and post-treatment vision. The Kruskal-Wallis test was used for comparison between the groups. All the groups were statistically comparable. All the eyes showed complete regression of CNV, with a minimum follow-up of six months. All groups had visual improvement; significantly in Group 3 ( p = 0.003. Combination PDT with anti-VEGF agents appeared to be efficacious in eyes with myopic CNV. However, a larger study with a longer follow-up is required to validate these results.

  15. Predictors of 1-year visual outcome in neovascular age-related macular degeneration following intravitreal ranibizumab treatment

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; la Cour, Morten; Sander, Birgit

    2013-01-01

    and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4-week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best-corrected visual acuity (BCVA...

  16. Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

    Institute of Scientific and Technical Information of China (English)

    Franck; Amouyal; Danièle; Denis; Frédéric; Matonti

    2014-01-01

    Dear Sir,Ifound the article by Sobac1etal[1]very interesting.The authors concluded that repeated intravitreal injection(IVI)of ranibizumab or bevacizumab didn’t seem have adverse effects on retinal nerve fiber layer(RNFL)thickness in wet age-related macular degeneration(AMD)patients.

  17. Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector.

    Science.gov (United States)

    Hayakawa, Natsumi; Abe, Manami; Eto, Risa; Kato, Hiroyuki; Araki, Tsutomu

    2008-06-01

    We investigated the age-related alterations in nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), parvalbumin and neuronal nitric oxide synthase (nNOS) immunoreactivity of the mouse hippocampal CA1 sector. NGF and BDNF immunoreactivity was unchanged in the hippocampal CA1 pyramidal neurons from 2 to 50-59 weeks of birth. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector from 40-42 to 50-59 weeks of birth. On the other hand, the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. Our results indicate that NGF and BDNF immunoreactivity was unaltered in the hippocampal CA1 pyramidal neurons during aging processes. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector during aging processes. The present study also shows that the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. These results demonstrate that the expression of glial NGF and BDNF may play a key role for helping survival and maintenance of pyramidal neurons and neuronal functions in the hippocampal CA1 sector during aging processes. Furthermore, our findings suggest that parvalbumin- and nNOS-positive interneurons in the hippocampal CA1 sector are resistant to aging processes. Moreover, our findings suggest that nitric oxide synthesized by the nNOS may play some role for neuronal growth during postnatal development.

  18. 神经生长因子与糖尿病神经病变的研究进展%Research Progress in NGF and Diabetic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    贾彩霞; 王元松

    2012-01-01

    Diabetic neuropathy is one of the common complications in diabetes. Nerve growth factor ( NGF )is important in the occuruence and development of diabetic neuropathy. NGF is a signal molecule the activity is regulated by tyrosine kinase receptor and p75 neurotrophin receptor. NGF can regulate central and periheral nerve growth and survival; and nerve growth factor can selectively nuture small nerve fibres sensory neurons and sympathetic neurons. In the anmial experiments and clinical studies, lots of evidence shows that NGF is closely related with diabetic neuropathy. It is useful to research the relationship between NGF and diabetic neuropathy for new perspectives for prevention and treatment of diabetic neuropathy.%糖尿病神经病变是糖尿病常见并发症之一.神经生长因子(NGF)在糖尿病神经病变的发生和发展中发挥重要作用.NGF是一种信号分子,其生物活性受酪氨酸激酶受体A和p75神经营养因子受体的调节.NGF能调节中枢神经和外周神经的生存和生长,并且NGF能选择性地营养小神经纤维感觉神经元和交感神经元.在动物模型和临床研究中,均有证据表明NGF与糖尿病神经病变关系密切.研究NGF与糖尿病神经病变的关系将有助于为糖尿病神经病变的防治提供新的研究思路.

  19. Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation

    DEFF Research Database (Denmark)

    Emdal, Kristina B; Pedersen, Anna-Kathrine; Bekker-Jensen, Dorte B

    2015-01-01

    SH-SY5Y neuroblastoma cells respond to nerve growth factor (NGF)-mediated activation of the tropomyosin-related kinase A (TrkA) with neurite outgrowth, thereby providing a model to study neuronal differentiation. We performed a time-resolved analysis of NGF-TrkA signaling in neuroblastoma cells...... then becomes phosphorylated and ubiquitylated and decreases in abundance. We also found that recruitment of Cbl-b promotes TrkA ubiquitylation and degradation. Furthermore, the amount of phosphorylation of the kinase ERK and neurite outgrowth increased upon Cbl-b depletion in several neuroblastoma cell lines...

  20. Phosphorylation of the growth factors bFGF, NGF and BDNF: a prerequisite for their biological activity.

    Science.gov (United States)

    Klumpp, Susanne; Kriha, Dorothee; Bechmann, Gunther; Maassen, Alexander; Maier, Sandra; Pallast, Stefanie; Hoell, Patrick; Krieglstein, Josef

    2006-01-01

    The aim of this work was to test whether growth factors such as basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) undergo autophosphorylation and whether this affects their biological activity. Incubation of those growth factors with [gamma-(32)P]ATP resulted in phosphorylation in vitro. The phosphate bond was resistant to alkaline pH, yet acid-labile. Addition of alkaline phosphatase resulted in time and protein dependent dephosphorylation. Concomitantly, alkaline phosphatase abolished the neuroprotective effect of those growth factors upon oxygen and glucose deprivation and upon staurosporine-induced cell death. For those studies, we were using primary cultures of cortical and hippocampal neurons from embryonic and neonatal rats. Incubation of bFGF with non-hydrolyzable ATP-gammaS resulted in phosphorylation and in neuroprotection resistant to alkaline phosphatase. We conclude that bFGF, NGF and BDNF undergo autophosphorylation on site(s) other than serine, threonine, tyrosine and/or ATP-binding, and that this binding of phosphate is essential for neuroprotection in vivo.

  1. Effects of castration on the immunoreactivity to NGF, BDNF and their receptors in the pelvic ganglia of the male rat

    Directory of Open Access Journals (Sweden)

    C Squillacioti

    2009-08-01

    Full Text Available Nerve growth factor (NGF and brain derived neurotrophic factor (BDNF and are members of the neurotrophin family, a family of neurotrophic factors that also includes neurotrophin (NT 3 and NT4/5. Neurotrophins have essential roles in the survival, development and differentiation of neurons in the central and peripheral nervous systems. Neurotrophins exert their effects by binding to corresponding receptors which are formed by the tyrosine protein kinases TrkA, TrkB and TrkC, and the low affinity neurotrophic receptor (p75NTR. In the present study, using immunohistochemistry and quantitative analysis, we have investigated immunoreactivity to BDNF, NGF, TrkB, p75NTR and TrkA in the pelvic ganglia of normal and castrated rats. Neurons of the pelvic ganglia expressed both these neurotrophins and their receptors. After castration the immunoreactivity persisted. However, the number of BDNF- and p75NTR–IR cells statistically significant decreased after castration. These results suggest that castration modulates the expression of neurotrophins and their receptors in pelvic autonomic neurons.

  2. Intravitreal bevacizumab for macular edema due to proton beam radiotherapy: Favorable results shown after eighteen months follow-up

    Directory of Open Access Journals (Sweden)

    Eleni Loukianou

    2010-05-01

    Full Text Available Eleni Loukianou, Dimitrios Brouzas, Eleni Georgopoulou, Chrysanthi Koutsandrea, Michael ApostolopoulosEye Department, University of Athens, Athens, GreecePurpose: To evaluate the safety and efficacy of intravitreal injections of bevacizumab (Avastin® as a treatment option for radiation maculopathy secondary to proton beam radiotherapy for choroidal melanoma.Case: A 61-year-old woman presented with a gradual decrease in left eye visual acuity (VA 29 months after proton beam radiotherapy for choroidal melanoma. On presentation, her best-corrected VA (BCVA was 2/10 in the left eye and the intraocular pressure was 15 mmHg. Fundoscopy revealed cystoid macular edema, intraretinal hemorrhages, epiretinal membrane in the posterior pole, and residual tumor scar with exudative retinal detachment and hard exudates in the periphery of the superotemporal quadrant. A treatment with intravitreal injections of bevacizumab (Avastin® was recommended. The injections were performed on a six-weekly basis.Results: The central retinal thickness prior to the treatment was 458 μm. After the first intravitreal injection of bevacizumab, the retinal thickness at the centre of the fovea was reduced to 322 μm. After the third injection, the central retinal thickness was 359 μm and 18 months after presentation, it reduced to 334 μm. The BCVA increased to 3/10 after the intravitreal injections of bevacizumab and remained stable during the follow-up period. The intraocular pressure was within normal range during the follow-up period.Conclusion: Bevacizumab should be regarded as a treatment option for macular edema due to proton beam radiotherapy for choroidal melanoma. By reducing the central retinal thickness, intravitreal bevacizumab can improve VA or ameliorate further decline caused by radiation maculopathy.Keywords: bevacizumab (Avastin®, choroidal melanoma, macular edema, radiation retinopathy

  3. Intravitreal injection with Ranibizumab combined with laser therapy for macular edema caused by branch retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Cong Zhang

    2014-08-01

    Full Text Available AIM:To investigate the efficacy of intravitreal ranibizumab combined with laser therapy in the treatment of macular edema caused by branch retinal vein occlusion(BRVO. METHODS:There were 78 patients(78 eyeswho were diagnosed with macular edema caused by BRVO using fundus fluorescence angiography(FFAand optical coherence tomography(OCT. Group A: randomly selected 26 cases(26 eyeswere given grid laser photocoagulation(GLP. Group B: randomly selected 26 cases(26 eyeswere given GLP first, and then received intravitreal ranibizumab 1wk later. Group C: randomly selected 26 cases(26 eyesundergone intravitreal ranibizumab first, and then given GLP 1wk later. There was no significant difference in macular edema. We analyzed the changes in the best corrected visual activity(BCVA, central macular thickness(CMTbefore and 1wk, 1,6mo after treatment. RESULTS: Compared with before treatment, 1wk after treatment: mean value changes of BCVA and CMT were no significant difference in group A(P>0.05; mean value changes of BCVA was improved and mean value of CMT was decreased in groups B and C, the difference was statistically significant(PPPPP>0.05between groups A and B after 6mo treatment; mean BCVA improved and CMT average value was decreased in group C, the difference was statistically significant(PPCONCLUSION: Intravitreal injection ranibizumab combined laser therapy can effectively reduce BRVO induced macular edema, enhance vision acuity. Compared with GLP, combination therapy has more rapid onset of treatment, and reduce macular edema better; Intravitreal ranibizumab should be given in front of the GLP, and the treatment effect is more precise, more stability.

  4. Intravitreal bevacizumab treatment for choroidal neovascularization in pathologic myopia: 12-month results.

    Science.gov (United States)

    Gharbiya, Magda; Allievi, Francesca; Mazzeo, Luigi; Gabrieli, Corrado Balacco

    2009-01-01

    To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of myopic choroidal neovascularization (CNV). Prospective, nonrandomized, interventional case series. Twenty eyes from 20 patients with CNV secondary to pathologic myopia participated in this prospective nonrandomized interventional case series. All patients were scheduled for three monthly intravitreal bevacizumab 1.25 mg injections. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 12 months. The mean BCVA (+/- standard deviation [SD]) at baseline was 24.8 (+/- 11.86) letters (Snellen equivalent: 20/80). At 12 months after treatment, the mean BCVA (+/- SD) improved significantly (P = .000001) to 43 (+/- 12.38) letters (Snellen equivalent: 20/35). At 12 month follow-up, BCVA improved 10 letters or more in 18 (90%) out of 20 treated eyes and improved 15 letters or more in 14 (70%) out of 20 treated eyes. No treated eyes experienced a worsening of BCVA from baseline. The mean FCT (+/- SD) at baseline was 223 (+/- 47.43) microns. At 12 months after treatment, the mean FCT (+/- SD) reduced to 206 (+/- 50.87) microns. This reduction in FCT after treatment was not statistically significant (P = .11). At 12 months follow-up, absence of fluorescein leakage from the CNV was demonstrated in 19 (95%) out of 20 treated eyes and persistent leakage in one eye (5%). None of the 19 eyes that had CNV closure experienced recurrence at 12-month follow-up. No ocular or systemic adverse effects from treatment were encountered. These results of intravitreal bevacizumab in myopic CNV are very promising with no apparent short-term safety concerns. At 12 months, treated eyes had a significant improvement in visual acuity (VA). OCT findings, as well, showed a trend consistent with the

  5. Intravitreal bevacizumab combined with plaque brachytherapy reduces melanoma tumor volume and enhances resolution of exudative detachment

    Directory of Open Access Journals (Sweden)

    Houston SK

    2013-01-01

    Full Text Available Samuel K Houston,1 Nisha V Shah,1 Christina Decatur,1 Marcela Lonngi,1 William Feuer,1 Arnold M Markoe,2 Timothy G Murray1–31Department of Ophthalmology, 2Department of Radiation Oncology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 3Murray Ocular Oncology and Retina, Miami, FL, USABackground: The purpose of this study was to evaluate intravitreal bevacizumab as an adjuvant treatment to plaque brachytherapy in the treatment of choroidal melanoma.Methods: This was a retrospective, consecutive study of 124 patients treated from 2007 to 2009 for choroidal melanoma with plaque brachytherapy. Patients were treated with I-125 plaque brachytherapy with 2 mm margins and 85 Gy to the tumor apex. Consecutive patients were injected intravitreally with 2.5 mg/0.1 mL bevacizumab at a site away from the primary tumor and immediately following plaque removal. Choroidal melanomas were observed using indirect ophthalmoscopy, wide-angle photography, and ultrasound. The main outcome measures were tumor volume, resolution of exudative retinal detachment, and visual acuity.Results: One hundred and twenty-four patients met our inclusion criteria and were included in the analysis. The mean patient age was 65.7 years, and the mean apical tumor height was 4.0 ± 2.7 mm and basal diameter was 12.7 ± 3.0 mm. Mean follow-up was 24 months. Prior to treatment, 100% of tumors had exudative retinal detachment, and pretreatment visual acuity was 20/55 (median 20/40. Tumor control was 100%, metastasis was 0% at last follow-up, and 89.8% had complete resolution of exudative retinal detachment, with a mean time to resolution of 3.36 months. At one month, 43% had complete resolution of exudative retinal detachment, which increased to 73% at 4 months. Visual acuity was 20/62 (median 20/40 at 4 months, with stabilization to 20/57 (median 20/40 at 8 months, 20/56 (median 20/30 at 12 months, and 20/68 (median 20/50 at 24 months. Tumor

  6. Strategies for Improving Patient Comfort During Intravitreal Injections: Results from a Survey-Based Study.

    Science.gov (United States)

    Gomez, Jessica; Koozekanani, Dara D; Feng, Alex Z; Holt, Mitchell; Drayna, Paul; Mackley, Melissa R; van Kuijk, Frederik J G M; Beardsley, Robert M; Johnston, Richard H; Terry, Joseph M; Montezuma, Sandra R

    2016-12-01

    Many ocular diseases require intravitreal injections of pharmacological agents. Optimizing patients' experiences during injections is important to ensure compliance and maintenance of quality of life. The objective of this study was to identify strategies to help alleviate discomfort during intravitreal injections. A cross-sectional study surveying 128 patients during clinic visits between 2014 and 2015 in two outpatient Retina Clinics (one academic and one private). Patients receiving an intravitreal injection(s) for any retinal disorder were given a questionnaire with 10-yes/no responses for various potential strategies. Responses were stratified by sex, age (60 years) and total number of prior injections (0-9 injections, 10-20 injections and >20 injections). A total of 128 patients were surveyed: 59 males, 41 females and 28 with no sex specified. Our results identified four favorable strategies as those receiving more than 50% "yes" votes. These included the presence of technician/staff during the procedure, the use of a neck pillow, a verbal warning before the injection and performing injections in both eyes on the same day. Other specific strategies were identified for females, younger patients and those with greatest experience. These included: females preferred having their hand held during injections (P = 0.001) and using a stress ball (P = 0.000) when compared to males. Stratifying by age, patients 30-60 years old preferred having their hand held (P = 0.008) and background music (P = 0.007). Stratifying by prior injections, patients with >20 prior injections preferred having their hand held (P = 0.001), using a stress ball (P = 0.021) and, if necessary, having bilateral injections performed the same day to improve comfort (P = 0.037). Having an extra staff member present during the injection, having a neck pillow, having a verbal warning prior to injection and having both eyes injected on the same day were indicated as favorable strategies

  7. Role of intravitreal Bevacizumab Injection for Management of Neovascular Age Related Macular Degeneration

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    Neha K Desai

    2016-06-01

    Full Text Available Background: Age related macular degeneration ( ARMD is the major cause of severe visual loss in older adults. Different treatment modalities are available such as: Laser photocoagulation, photodynamic therapy,transpupillary thermotherapy,submacular surgery and anti-veg. Aims and Objectives: The aim of our study was to evaluate the efficacy and safety of intravitreally administered Bevacizumab a humanized monoclonal anti and ndash;VEGF in Neovascular Age related Macular Degeneration. Methodology: This non randomized, prospective study was carried out on 75 eyes of 75 patients attending the OPD at M and J Institute Of Ophthalmology and diagnosed as having Neovascular ARMD confirmed on FFA and SD-OCT . After taking written informed consent all patients were injected with intravitreal Bevacizumab 1.25 mg/0.05 ml. Follow up visits were scheduled one week, one month post procedure and every monthly thereafter. Results: 75 eyes of 75 patients were included in this non randomized prospective study. and 29.33% patients required 2 injections. Visual acuity is improved more than 3 lines from baseline in 21.33% patient, 64% patient have 2-3 lines gain and 6.66% patients showed 0-1 line gain in snellen's visual acuity. 5.33% patients have a loss of 1 line from baseline and 2.66% patients showed loss of 2-3 lines. Central foveal thickness decreased more than 200 microns from baseline in 52% patients, 28% patients have decreased of 100-200 microns and 20% patients have decreased of less than 100 microns. Discussion: Approximately 10 % of ARMD patients manifest the neovascular form of the disease. 12 weeks. Our study showed that 80% patients had decrease in central foveal thickness more than 100 microns from baseline at the end of one year. 85% patients had gain of 2 or more lines on Snellen's visual acuity chart from baseline.No patient had any serious local or systemic adverse reactions.Limitations of our study is small number of patients,ICG not done

  8. Visual outcome of intravitreal ranibizumab for exudative age-related macular degeneration: timing and prognosis

    Directory of Open Access Journals (Sweden)

    Canan H

    2014-01-01

    Full Text Available Handan Canan,1 Selçuk Sizmaz,2 Rana Altan-Yaycioğlu,1 Çağla Saritürk,3 Gürsel Yilmaz41Department of Ophthalmology, Adana Teaching and Medical Research Center, Baskent University School of Medicine, 2Department of Ophthalmology, Çukurova University School of Medicine, 3Department of Biostatistics, Adana Teaching and Medical Research Center, Baskent University School of Medicine, 4Department of Ophthalmology, Baskent University School of Medicine, Ankara, TurkeyPurpose: To describe 1-year clinical results of intravitreal ranibizumab treatment in patients with choroidal neovascularization secondary to exudative age-related macular degeneration (AMD and to evaluate whether early treatment is a predictive value for prognosis of the disease.Materials and methods: Clinical records were retrospectively reviewed of 104 eyes that underwent intravitreal ranibizumab therapy for exudative AMD. Patients were divided into two groups according to their symptom duration: group 1, <1 month; and group 2, 1–3 months. After three monthly injections, patients were examined monthly, and subsequent injections were performed as needed.Results: There were 43 female (48.9% and 45 males (51.1%. The follow-up time was 13.7±1.9 (12–19 months. The mean logarithm of minimum angle of resolution best-corrected visual acuity (BCVA improved significantly, from 0.45±0.639 at baseline to 0.08±0.267 at 12 months in group 1, and from 1.06±0.687 at baseline to 0.75±0.563 at 12 months in group 2. The increase in BCVA was statistically significant in group 1 (P=0.009. The mean central retinal thickness (CRT decreased significantly, from 355.13±119.93 µm at baseline to 250.85±45.48 µm at 12 months in group 1, and from 371.88±91.047 µm at baseline to 268.61±53.51 µm at 12 months in group 2. The decrease in CRT was statistically significant in group 1 (P=0.001.Conclusion: Intravitreal ranibizumab therapy was effective in significantly increasing mean BVCA and

  9. Biomaterial of [PEAD: Heparin: NGF] Coacervate Promote Function Recovery of Sciatic Nerve Regeneration in Rats%[PEAD:肝素:NGF]生物材料促进大鼠坐骨神经损伤恢复

    Institute of Scientific and Technical Information of China (English)

    李锐; 蔡平讨; 叶丽冰; 张宏宇; 肖健

    2016-01-01

    目的:探讨新型材料poly(ethylene argininylaspartate diglyceride)(PEAD)结合肝素包裹神经生长因子组成的三元复合体比单纯运用NGF治疗大鼠坐骨神经损伤效果明显,为临床治疗外周神经损伤提供实验依据.方法:24只200g左右Wistar大鼠,分成生理盐水组,NGF组,NGF凝聚体三组,每组各8只,距梨状肌下缘远侧约1.5cm处运用静脉夹夹紧坐骨神经2min,采用无创细线(5/0)缝合肌肉和皮肤,并用碘伏进行消毒,NGF组每天沿坐骨切迹肌注80ngNGF,持续30天;NGF凝聚体组仅在造模时肌注[PEAD:肝素:NGF]复合体(内含2.4μg的NGF);生理盐水组给予等体积的生理盐水.术后每周运用脚步印迹法评价动物的行为学,并于30天后灌流、收集各组损伤侧坐骨神经,运用HE染色及投射电镜观察坐骨神经结构恢复情况,免疫荧光标记MBP,观察其蛋白的表达.结果:NGF组,NGF凝聚体组在行为学、病理结构及蛋白的表达远高于生理盐水组,并且NGF凝聚组的治疗效果优于NGF组.结论:新型凝聚体[PEAD:肝素]包载NGF具有明显的促进周围神经损伤后的修复与再生作用,能够在一定程度上提高单纯运用NGF治疗大鼠坐骨神经损伤的不足,达到更加理想和显著的促恢复效果.

  10. Juxtapapillary neovascular membrane secondary to idiopathic intracranial hypertension treated with intravitreal bevacizumab: A case report.

    Science.gov (United States)

    Hernández-Ortega, V; Soler-Sanchís, M I; Jiménez-Escribano, R M; Sanz-López, A M

    2016-05-01

    A 48 year-old woman with visual acuity loss in left eye (0.3). Funduscopic examination showed papillary oedema and neovascular membrane in the left eye. All neurological tests were normal, except the lumbar puncture with opening pressure of 35cmH2O, being diagnosed with idiopathic intracranial hypertension (IIH). After four doses of bevacizumab, the visual acuity of the left eye has not improved and is counting fingers. Pathogenesis of the juxtapapillary neovascular membrane associated with IIH is not well known. An effect was observed after the anti-VEGF treatment. In our case, there was no improvement after four doses of intravitreal bevacizumab. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  12. Pharmacokinetics of intravitreal glial cell line-derived neurotrophic factor: experimental studies in pigs

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Kiilgaard, J F; Tucker, B A;

    2010-01-01

    The purpose of this study was to establish the intravitreal (ITV) pharmacokinetics of glial cell line-derived neurotrophic factor (GDNF) and observe possible complications after ITV injection. Twenty Danish landrace pigs and 34 eyes were included in the study; 30 were injected with 100 ng of GDNF......, two controls were injected without GDNF, and two received no injection. At post-injection time points of 1, 2, 3, 6 hours (h), 1, 2, 4 or 7 days (d) eyes were enucleated and the ITV concentration of GDNF (cGDNF) was determined by enzyme-linked immunosorbent assay, and activity was tested using...... a retinal ganglion cell line (RGC5) bioassay. Indirect ophthalmoscopy, intraocular pressure assessment, and fundus photography were performed before enucleation. There was initial variability in the cGDNF, but after 24h GDNF was cleared in a monoexponential fashion with a half-life of 37 h (CL 33-43 h...

  13. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

    2008-01-01

    , pilot study of 26 eyes of 26 patients, all previously treatment-naive to photodynamic therapy, argon laser or anti-vascular endothelial growth factor (VEGF), were treated with one or more intravitreal injections of 1.25 mg bevacizumab. Of the 26 patients, 15 (57.7%) had occult choroidal...... neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5 (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast sensitivity and OCT. The patients were examined at baseline and 1 week, 6 weeks, 3...... months and 6 months after the first injection. Re-treatment was given on an 'as needed' basis. Results: Twenty-four eyes of 24 patients completed 6 months of follow-up. Two patients chose to discontinue the study. Mean ETDRS VA score improved from 55 letters at baseline to 60 letters at 1 week (P

  14. Subconjunctival and Orbital Silicone Oil Granuloma (Siliconoma Complicating Intravitreal Silicone Oil Tamponade

    Directory of Open Access Journals (Sweden)

    Jung Hye Lee

    2014-01-01

    Full Text Available A 30-year-old male, who underwent previous pars plana vitrectomy and silicone oil tamponade due to endogenous endophthalmitis originated from Klebsiella liver abscess, was referred for evisceration. At 2 months after vitrectomy with silicon oil tamponade, conjunctival chemosis and ocular pain were aggravated. Diffuse eyelid swelling and large subconjunctival mass with lipid droplets were noted. On MRI examination, subconjunctival mass and intra- and extraconal orbital mass around superior rectus muscle were observed. Excision of subconjunctival and orbital mass was performed. Histopathologic examination showed multiple silicone oil vacuoles surrounded by foreign body giant cells and fibrosis, which confirmed silicone oil granuloma. In a patient with suspicious melting sclera in diseases such as endophthalmitis, large silicone oil granuloma may be complicated in a rapid fashion after intravitreal silicone oil tamponade due to silicone oil leakage.

  15. Steerable intravitreal inserts for drug delivery: in vitro and ex vivo mobility experiments.

    Science.gov (United States)

    Bergeles, Christos; Kummer, Michael P; Kratochvil, Bradley E; Framme, Carsten; Nelson, Bradley J

    2011-01-01

    The progress of wet age-related macular degeneration can now be controlled by intravitreal drug injection. This approach requires repeated injections, which could be avoided by delivering the drug to the retina. Intraocular implants are a promising solution for drug delivery near the retina. Currently, their accurate placement is challenging, and they can only be removed after a vitrectomy. In this paper, we introduce an approach for minimally invasive retinal drug delivery using magnetic intraocular inserts. We briefly discuss the electromagnetic-control system for magnetic implants and then focus on evaluating their ability to move in the vitreous humor. The mobility of magnetic intraocular implants is estimated in vitro with synthesized vitreous humors, and ex vivo with experiments on cadaver porcine eyes. Preliminary results show that with such magnetic implants a vitrectomy can be avoided.

  16. Progression of choroidal metastasis of ovarian serous cystoadenocarcinoma after intravitreal bevacizumab treatment

    Directory of Open Access Journals (Sweden)

    Victor E. Reviglio

    2013-02-01

    Full Text Available A 57-year-old woman presented to her ophthalmologist because of rapid deterioration in vision. Dilated funduscopic examination of the right eye showed an elevated, yellow-orange choroidal mass temporal to the fovea; a complete retinal detachment was present in the left eye. The patient was referred to an oncologist. Computerized tomography of the brain, thorax, abdomen, and pelvis were obtained. They revealed an 11-mm mass in the right parietal lobe, a 30-mm mass in the left temporal lobe, 23-mm mass in the right kidney, and multiple nodules in both lungs. Supported by published experience with intravitreal bevacizumab for choroidal metastasis, the patient was injected into the vitreous through the pars plana of the left eye. The tumor mass did not show signs of regression and the visual acuity was unchanged. The patient suffered from end-state complications tumor metastasis and expired one month after the invitreal injection.

  17. Flicker electroretinograms before and after intravitreal ranibizumab injection in eyes with central retinal vein occlusion.

    Science.gov (United States)

    Yasuda, Shunsuke; Kachi, Shu; Ueno, Shinji; Piao, Chang-Hua; Terasaki, Hiroko

    2015-09-01

    To compare the amplitudes and implicit times of the flicker electroretinograms before and after an intravitreal injection of ranibizumab (IVR) in eyes with a central retinal vein occlusion (CRVO). We reviewed the medical records of 15 consecutive patients who had macular oedema secondary to CRVO and had received an IVR at the Nagoya University Hospital from November 2013 to July 2014. Flicker ERGs were recorded with both the RETeval(™) system and a conventional ERG system before the IVR. One month after the IVR, recordings were repeated with only the RETeval(™) system. The mean implicit times of the flicker ERGs of the affected eyes recorded with the RETeval(™) system were significantly longer than that of the fellow eyes (32.2 ± 2.6 msec versus 28.1 ± 1.2 msec, p retinal function after anti-VEGF therapy for CRVO eyes. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  18. Intravitreal Triamcinolone Acetonide for Patients with Macular Edema due to Branch Retinal Vein Occlusion

    Directory of Open Access Journals (Sweden)

    Kai-Chun Cheng

    2006-07-01

    Full Text Available We designed a case series study to evaluate the outcome of intravitreal triamcinolone acetonide for the treatment of macular edema due to branch retinal vein occlusion (BRVO. The prospective comparative nonrandomized clinical interventional study included 27 patients (27 eyes with macular edema due to BRVO. The study group consisted of 16 patients who had accepted an intravitreal injection (IVI of 4 mg triamcinolone acetonide. The control group included 11 patients without IVI of triamcinolone acetonide. The mean follow-up was 103.00 36.24 days in the study group and 94.55 36.31 days in the control group. In the study group, visual acuity measurements improved significantly (p 0.001 from 0.77 0.43 logarithm of minimal angle of resolution (logMAR preoperatively to a best postoperative visual acuity of 0.44 0.43 logMAR. Fourteen eyes (87.5% gained improvement in visual acuity, with 10 eyes (62.5% showing an increase in visual acuity of at least two Snellen lines. All 16 patients showed significant macular edema resolution in optical coherence tomography examination (p 0.001 and perivascular leakage decrease in fluorescein angiography post-IVI. In the control group, baseline best-corrected visual acuity and best-corrected visual acuity during the follow-up did not vary significantly (p 0.294. In conclusion, IVI of triamcinolone acetonide can lead to an increase in visual acuity and a resolution of macular edema in patients with BRVO.

  19. INTRAVITREAL TRIAMCINOLONE IN DIABETIC MACULAR EDEMA : A COMPARATIVE STUDY OF 1 MG AND 4MG DOSES

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    Sikander A . K

    2015-06-01

    Full Text Available Macular edema is a frequent manifestation of diabetic retinopathy and animportant cause of visual disturbance in diabetic patients. AIM: To compare the efficacy and safety of 1mg and 4mg intravitreal triamcinolone acetonide (IVTA in the management of diabetic macular edema. SETTING: Sarojini Devi Eye Hospital, Hyderabad. MATERIAL AND METHODS: 42 eyes of 42 patients with diabetic macular edema were randomly assigned torecei ve either 1 - mg or 4 - mg dose of Intravitreal triamcinolone acetonide (IVTA. Each patient underwent a complete comprehensive eye examination at baseline andat each visit.Fundus fluorescein angiography and optical coherence angiographywas done at baseline an d at 1, 3 and 6 months.BCVA, lens status, IOP wererecorded at each follow up visit. Each patient’s BCVA was measured in snellen’s lines and converted into logarithm of minimum angle of resolution (log MAR scale for analysis. STATISTICAL ANALYSIS USED : The data were statistically evaluated using the Wilcoxon signedrank test, Mann - Whitney test and t tests wherever applicable. A p value of lessthan . 05 was considered significant. RESULTS: There was no statistically significant difference in the mean foveal thickness measurement at baseline (p=.723 or at 3 rd month (p=.878 between the sub - groups. BCVA significantly improved from baseline to subsequent visits in both the groups, but there was no statistically significant difference observed in the mean baseli ne BCVA between the two sub - groups (p=.754. There was no statistically significant difference observed in IOP between the two sub - groups at any follow up visit. CONCLUSIONS: The results of our study suggest that 1 - mg dose of IVTA is as effective as 4 - mgdo se of IVTA in improving the functional and anatomical outcome in macularedema associated with diabetic retinopathy.

  20. Ocular Decompression with Cotton Swabs Lowers Intraocular Pressure Elevation Following Intravitreal Injection

    Science.gov (United States)

    Gregori, Ninel Z.; Weiss, Matthew J.; Goldhardt, Raquel; Schiffman, Joyce C.; Vega, Edgardo; Mattis, Cherrie-Ann; Shi, Wei; Kelley, Linda; Hernandez, Vilma; Feuer, William J.

    2013-01-01

    Objective To determine the effect of pre-injection ocular decompression by cotton swabs on the immediate rise in intraocular pressure (IOP) after intravitreal injections. Methods Forty-eight patients receiving 0.05-ml ranibizumab injections in a retina clinic were randomized to two anesthetic methods in each eye on the same day (if bilateral disease) or on consecutive visits (if unilateral disease). One method utilized cotton swabs soaked in 4% lidocaine applied to the globe with moderate pressure and the other 3.5% lidocaine gel applied without pressure. IOPs were recorded at baseline (before injection) and at 0, 5, 10, and 15 minutes after the injection until the IOP was ≤30 mmHg. The IOP elevations from baseline were compared after the two anesthetic methods. Results The pre-injection mean IOP (SD, mmHg) was 15.5 (3.3) before the cotton swabs and 15.9 (3.0) before the gel (p=0.28). Mean IOP (SD, mmHg) change immediately after injection was 25.7 (9.2) after the cotton swabs and 30.9 (9.9) after the gel (P=0.001). Thirty-five percent of gel eyes had IOP ≥50 mmHg compared to only 10% of cotton swab eyes immediately after the injection (P<0.001). Conclusion Decompressing the eye with cotton swabs during anesthetic preparation prior to an intravitreal injection produces a significantly lower IOP spike after the injection. PMID:23632408

  1. Characteristics of Macular Edema in Behcet Disease after Intravitreal Bevacizumab Injection

    Science.gov (United States)

    Ghassemi, Fariba; Mirak, Sohrab Afshari; Chams, Hormoz; Sabour, Siamak; Ahmadabadi, Mehdi Nilli; Davatchi, Fereidoun; Shahram, Farhad

    2017-01-01

    Purpose: To investigate the effect of intravitreal bevacizumab (IVB) injection on macular edema (ME) secondary to Behcet's disease. Methods: This prospective case series included 15 patients with bilateral ME due to Behcet's disease. Intravitreal bevacizumab was injected into the more severely involved eye; the contralateral eye was evaluated as the control. Patients were followed up with comprehensive ocular examination, optical coherence tomography, and fluorescein angiography (FA) for a minimum of 6 months by a single ophthalmologist. Results: Patients with a mean age of 30.6 ± 7.4 years received a mean number of 3.3 IVB injections during the 6 months. The mean preinjection vision was 0.6 ± 0.3 and 0.4 ± 0.4 LogMAR in the case and control groups, respectively, with no significant improvement at 6 months. Mean central foveal thickness was 375.3 ± 132.1 and 307.2 ± 84.5 μm in the case and control groups, respectively, and these changed to 401 ± 199.9 (P = 0.65) and 307.7 ± 82.8 μm (P = 0.73) at month 6, respectively. A statistically nonsignificant improvement in ME was observed during the first 3 months in the case group. However, it did not persist up to month 6 on an as-needed basis. IVB injections caused a disproportionate decrease in the thickness of macular subfields. A reduction in disc leakage was observed on FA (P = 0.058). Logistic regression analysis revealed no statistically significant predictive factor for an improvement in visual acuity (VA) and a reduction in foveal thickness. Conclusion: During a 6-month period, IVB injections based on an as-needed protocol provided no statistically significant improvement in VA and ME. PMID:28299006

  2. Intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion.

    Science.gov (United States)

    Risard, Sarah M; Pieramici, Dante J; Rabena, Melvin D; Basefsky, Jessica C; Avery, Robert L; Castellarin, Alessandro A; Nasir, Ma'an A; See, Robert F; Couvillion, Stephen S

    2011-06-01

    To evaluate the safety and efficacy of intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion. Patients with macular edema secondary to perfused central retinal vein occlusion were enrolled in this ongoing, prospective, open-label study. Treatment was initiated with monthly intravitreal ranibizumab for 3 months. In the first year, additional injections were administered for edema in quarterly intervals as needed (PRN) for Cohort 1 (n = 10) and monthly PRN for Cohort 2 (n = 10). In the second year of treatments, all patients received monthly PRN treatment. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, central retinal thickness, fundus photographs, and fluorescein angiograms were evaluated, and the incidence and severity of adverse events were documented. Mean change in best-corrected visual acuity and central retinal thickness improved during the induction phase in both groups. During the remainder of the first year for Cohort 1, initial gains were lost during quarterly treatment but returned with monthly PRN treatment in the second year. For Cohort 2, improvement in best-corrected visual acuity and central retinal thickness from the induction phase was maintained through Month 24. Nineteen of 20 patients experienced a reduction in intraretinal hemorrhage, optic nerve swelling, and/or venous diameter after treatment. One myocardial infarction, one cerebrovascular accident, and no serious ocular adverse events were reported. Iris neovascularization was developed in none of the eyes. Ranibizumab was well tolerated and associated with a greater reduction in macular edema and improvement in visual acuity in the monthly PRN regimen compared with quarterly treatment. Vision lost during the quarterly PRN injection intervals in the first year of Cohort 1 could be regained by switching to monthly PRN dosing.

  3. Evaulation of Incidence and Risk Factors for Intraocular Pressure Elevation After Intravitreal Triamcinolone Acetonide Injection

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    Didar Uçar

    2015-05-01

    Full Text Available Objectives: To investigate the effect of intravitreal triamcinolone acetonide (IVTA used for the macular edema on intraocular pressure (IOP and to determine the risk factors for IOP elevation. Materials and Methods: This retrospective study included 93 eyes of 85 patients who had 4 mg intravitreal triamcinolone injection. Of the 85 patients, 56 (65.8% had diabetic macular edema, 22 (25.8% had branch retinal, and 7 (8.2% had central retinal vein occlusion. IOP changes after injection as well as the relation between IOP elevation and age, sex, lens status, etiology of macular edema, baseline IOP were evaluated. Results: Fourty-six male and 39 female patients with mean age 61.58±9.5 years were evaluated. IOP was recorded to be >24 mmHg in 30 eyes (32.2% at follow-up visit after an average of 7.5 weeks. Normalization of IOP with medication was achieved in all IOP elevated eyes. Fifteen of 29 eyes (51.7% with vein occlusion and 15 of 64 eyes (23.3% with diabetic macula edema had IOP elevation (p=0.01. Twenty-six of 73 phakic (35.6% and 4 of 20 pseudophakic eyes (20% had IOP >24 mmHg (p=0.16. There was no association between IOP elevation and sex (p=0.33. Baseline IOP was 16.47±2.8 mmHg in eyes which had elevated IOP and 14.78±2.4 mmHg in the remaining. There was significant relation between IOP elevation and baseline IOP level (p=0.01. Conclusion: Elevated IOP is common side effect after IVTA, but normalization is usually achieved by topical medication. Patients with baseline IOP ≥15 mmHg and vein occlusion have higher risk for IOP elevation. (Turk J Ophthalmol 2015; 45: 86-91

  4. Over-expression of hNGF in adult human olfactory bulb neural stem cells promotes cell growth and oligodendrocytic differentiation

    NARCIS (Netherlands)

    H.E.S. Marei (Hany); A. Althani (Asmaa); N. Afifi (Nahla); A. Abd-Elmaksoud (Ahmed); C. Bernardini (Camilla); F. Michetti (Fabrizio); M. Barba (Marta); M. Pescatori (Mario); G. Maira (Giulio); E. Paldino (Emanuela); L. Manni (Luigi); P. Casalbore (Patrizia); C. Cenciarelli (Carlo)

    2013-01-01

    textabstractThe adult human olfactory bulb neural stem/progenitor cells (OBNC/PC) are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases, h

  5. The exposure to nicotine affects expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in neonate rats.

    Science.gov (United States)

    Xiaoyu, Wang

    2015-02-01

    In the current study effect of nicotine on expression of neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) has been studied in hippocampus and frontal cortex during development of brain in rats. Neurotrophins are factors that help in development of brain among which BDNF and NGF are very important, expressed at different stages during the developmental process. Different sedatives are reported to alter the expression of these factors. In this study, three groups of neonate rats (1-5, 5-10 and 10-15 days age) were used each having 20 rats. Ten were subjected to a dose of 66 μg of nicotine while other ten received the same amount of saline at the same time interval. Then expression of the BDNF and NGF was observed in hippocampus and frontal cortex tissue using immunoassay. Western blotting was used to observe the presence of BDNF in hippocampus as well as frontal cortex. In all groups there was a significant decrease in concentration of neurotrophic factors where nicotine was applied as compared to control. The highest expression of BDNF and NGF in hippocampus and frontal cortex was observed in 10-15 days group (G3) and in 5-10 group (G2) as compared to the control, P BDNF and it effects the development of brain in neonates that can further impair brain functions.

  6. Establishing a cellular FRET-based fluorescence plate reader assay to monitor proNGF-induced cross-linking of sortilin and the neurotrophin receptor p75(NTR).

    Science.gov (United States)

    Skeldal, Sune; Kjaergaard, Maj M; Alwasel, Saleh; Nyengaard, Jens R

    2015-01-01

    Whereas the proform of the nerve growth factor (proNGF) is crucial for eliminating superfluous cells during neuronal development it also promotes apoptosis following brain trauma and neuronal injury. The apoptotic signal is elicited upon formation of a trimeric receptor complex also containing the vps10p domain receptor sortilin and the neurotrophin receptor p75(NTR). However, proNGF-induced receptor complex formation has been difficult to directly assess other than by western blotting. We here describe a fluorescence resonance energy transfer (FRET) based fluorescence plate reader assay to monitor the interaction between fluorescently tagged sortilin and p75(NTR) in live cells. The method is based on a standard fluorescent plate reader found in many biochemical laboratories and the results are evaluated using a microscopy-based quantified sensitized acceptor emission FRET approach making use of a pair of FRET standard constructs. As a result, the effect of proNGF on the interaction between sortilin and p75(NTR) can be evaluated in live cells allowing for screening and selection of therapeutic compounds interfering with proNGF-induced cell death.

  7. Immunolocalization of NGF and its receptors in ovarian surface epithelium of the wild ground squirrel during the breeding and nonbreeding seasons.

    Science.gov (United States)

    Bao, L; Li, Q; Liu, Y; Li, B; Sheng, X; Han, Y; Weng, Q

    2014-05-09

    The ovarian surface epithelium (OSE) plays an important role in normal ovarian physiology. During each reproductive cycle, the OSE takes part in the cyclical ovulatory ruptures and repair. The aim of this study was to investigate the immunolocalization of nerve growth factor (NGF) and its receptors, tyrosine kinase A (TrkA) and p75, in the OSE cells of the wild ground squirrels during the breeding and nonbreeding seasons. There were marked variations in ovarian weight and size between the breeding and the nonbreeding seasons. Histologically, cuboidal cells and squamous cells were identified in the OSE of both seasons. Yet, stronger immunostaining of NGF, TrkA and p75 were observed in cuboidal cells and squamous cells in the breeding season as compared to the nonbreeding season. In addition, plasma gonadotropin concentrations were higher in the breeding season than in the nonbreeding season, suggesting that the expression patterns of NGF, TrkA and p75 in the OSE were correlated with changes in plasma gonadotropins. These findings suggested that NGF and its receptor TrkA and p75 may be involved in the regulation of seasonal changes in the OSE of wild ground squirrel.in the OSE of wild ground squirrel.

  8. A comparative morphological, electrophysiological and functional analysis of axon regeneration through peripheral nerve autografts genetically modified to overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF

    NARCIS (Netherlands)

    Hoyng, Stefan A; De Winter, Fred; Gnavi, Sara; de Boer, Ralph; Boon, Lennard I; Korvers, Laura M; Tannemaat, Martijn R; Malessy, Martijn J A; Verhaagen, J.

    2014-01-01

    The clinical outcome of microsurgical repair of an injured peripheral nerve with an autograft is suboptimal. A key question addressed here is: can axon regeneration through an autograft be further improved? In this article the impact of six neurotrophic factors (BDNF, CNTF, GDNF, NGF, NT3 or VEGF) o

  9. Intravitreal bevacizumab versus triamcinolone acetonide for macular edema due to branch retinal vein occlusion: a matched study

    Institute of Scientific and Technical Information of China (English)

    HOU Jing; TAO Yong; JIANG Yan-rong; LI Xiao-xin; GAO Lei

    2009-01-01

    Background Branch retinal vein occlusion (BRVO) is a common retinal vascular disorder of the elderly and both intravitreal triamcinolone acetonide (TA) and intravitreal bevacizumab were reported to be effective. The purpose of this study was to compare intravitreal bevacizumab with intravitreal TA for the treatment of macular edema resulting from BRVO.Methods The retrospectively comparative interventional study included a bevacizumab group of 34 BRVO patients (1.25 mg bevacizumab) and a TA group of 34 BRVO patients (4.0 mg TA), and the two groups were matched by baseline best corrected visual acuity (BCVA). Examinations were designed to be carried out at 1 day, 3 days, 1 month, 2 months, 3 months, 6 months and 1 year after each injection. The mean follow-up was (148.43±130.56) days. Main outcome parameters were BCVA and morphometric measurements of the macula obtained by optical coherence tomography.Results In all follow-ups, the mean changes of BCVA (LogMAR) between two groups were not significantly different (P >0.10). Similarly, the rates of patients who got BCVA improvement >2 lines or lost BCVA >2 lines were not significantly different, either (P >0.10). In both groups, compared with baseline, the mean central macular thickness (CMT) got reduction from 4 weeks to 1 year after initial injection, however, which lost statistical significance at 6-month follow-up in TA group (P=0.25) and lost significance at 3-month and 6-month follow-up in bevacizumab group (P=0.07, 0.21). The mean CMT between two groups differed at 3-month follow-up (P 0.40). In TA group, retinal pigment epithelium tear occurred in 1 eye at 8 weeks after initial injection and 12 eyes (35.3%) got intraocular pressure >21 mmHg. In bevacizumab group, no severe complications were observed.Conclusion For BRVO, intravitreal bevacizumab versus intravitreal TA causes a similar increase in visual acuity and reduction of macular edema (except 3-month follow-up) with minor complications during 1 year.

  10. NGF体外对精子活力的影响%Effect of NGF on the sperm motility of human in vitro

    Institute of Scientific and Technical Information of China (English)

    林凯; 石翠格; 赵永岐; 刘淑红; 范明

    2012-01-01

    Objective Motility is an important physiological characteristic of a mature sperm.Nerve growth factor(NGF) is a protein essential for the development,maintenance and survival of the peripheral and central nervous systems.NGF and its receptors TrkA and p75 are widely expressed in the testis,accessory reproductive organ,and the epididymal sperms.In the present study,we investigated the role of NGF on human sperm motility.Methods Use 0.1,1 and 10 μmol/L concentrations of NGF,on sperm motility study to investigate the optimal concentration.Use CASA to detect Sperm motility changes every 10 minutes in an hour after 10 μmol/L NGF was added to the semen.Results The parameters of sperm motility increased after NGF incubation had significant difference, in particular,VAP,VSL,VCL,BCF and LIN mean were significantly increased more than 32%.MAD,STR,ALH and WOB mean had no notable difference.Furthermore,NGF promotes the sperm motility in a time- and dose- dependent manner.In addition,the enhancement of NGF on sperm motility was more stronger than those of sperm culture medium.Conclusion Our findings suggest that NGF plays a promoted role in human sperm motility.%目的 观察神经生长因子(NGF)体外对精子活力的影响,确定NGF的最佳量效和时效关系,探索NGF体外对精子活力的影响以及和男性不育的关系.方法 分别用0.1、1、10 μmol/L的NGF对精子活力进行研究,以探讨最佳浓度.将10 μmol/L NGF加入精液中在1 h内每隔10 min用CASA检测精子的活力变化.结果 NGF可显著增加精子的平均速率、直线速率、曲线速率和线性系数,差异有统计学意义(P<0.01);增加鞭打频率差异有统计学意义(P<0.05).1 μmol/L的NGF和0.1 μmol/L的NGF对精子活力的促进作用相比有统计学差异,10 μmol/L浓度组和1 μmol/L浓度组差异没有统计学意义.NGF反应30 min后对精子活力的影响最大,一直保持到1 h以后.结论 外源性给予NGF可显著增加健康人和不育症

  11. Ovulation-inducing factor (OIF/NGF) from seminal plasma origin enhances Corpus Luteum function in llamas regardless the preovulatory follicle diameter.

    Science.gov (United States)

    Silva, M; Ulloa-Leal, C; Norambuena, C; Fernández, A; Adams, G P; Ratto, M H

    2014-08-01

    Ovulation-inducing factor (OIF) is a protein present in llama seminal plasma that has recently been identified as β-Nerve Growth Factor (NGF) and it induces not only a high rate of ovulation but also appears to have luteotrophic properties in this species. A 2-by-2 experimental design was used to determine the effect of treatments (OIF/NGF vs GnRH) and categories of preovulatory follicle diameter (7-10 vs >10mm) on ovulation rate, CL diameter and function in llamas. Llamas (n=32 llamas per group) were randomly assigned to receive an intramuscular dose of: (a) 1mg purified OIF/NGF in the presence of a follicle of 7-10mm in diameter; (b) 50 μg of GnRH in the presence of a follicle of 7-10mm in diameter; (c) 1mg purified OIF/NGF in the presence of a follicle >10mm in diameter; (d) 50 μg of GnRH in the presence of a follicle >10mm in diameter. Llamas were examined by ultrasonography every 12h from treatment to Day 2 (Day 0=treatment) to detect ovulation, and again on Day 8 to determine CL diameter. Ovulation rates did not differ among groups. There was an effect of preovulatory follicle size on Corpus Luteum diameter at Day 8 (PNGF - than that of the GnRH - treated group by the same day. We conclude that OIF/NGF treatment enhances CL function regardless preovulatory follicle size at the time of treatment.

  12. Successful use of intravitreal and systemic colistin in treating multidrug resistant Pseudomonas aeruginosa post-operative endophthalmitis

    Directory of Open Access Journals (Sweden)

    Preetam Samant

    2014-01-01

    Full Text Available We report a case series of post-operative endophthalmitis due to Pseudomonas aeruginosa. A total of 8 patients operated for cataract, were referred to our facility with acute onset of decreased vision 1-2 days following surgery. All patients had clinical evidence of acute exogenous endophthalmitis with severe anterior chamber exudative reaction. Ocular samples (aqueous aspirate and vitreous tap for microbiology were taken from all eyes. Microbiology from all revealed P. aeruginosa which was resistant to all antibiotics except colistin. With prompt and accurate microbiological support it was possible to control the infection in all the eyes with the use of colistin intravitreally and intravenously which to the best of our knowledge, has been never reported. Intravitreal injection of colistin could be an option effective in the management of multi-drug-resistant endophthalmitis caused by Gram-negative bacteria.

  13. Effect of prophylactic timolol 0.1% gel on intraocular pressure after an intravitreal injection of ranibizumab: a randomized study

    OpenAIRE

    Pece A; Allegrini D; Montesano G; Dimastrogiovanni AF

    2016-01-01

    Alfredo Pece,1 Davide Allegrini,1 Giovanni Montesano,2 Andrea Fabio Dimastrogiovanni1 1Eye Clinic, Melegnano Hospital, Vizzolo Predabissi, 2Eye Clinic, San Paolo Hospital, Università di Milano, Milano, Italy Purpose: The purpose of this study is to make a prospective evaluation of the effect of timolol 0.1% eye gel on short-term intraocular pressure (IOP) after an intravitreal injection (IVI) of ranibizumab. Participants and methods: One hundred and fifty eyes of 150 IVI-na&i...

  14. Degranulation, density, and distribution of mast cells in the rat thalamus: a light and electron microscopic study in basal conditions and after intracerebroventricular administration of nerve growth factor.

    Science.gov (United States)

    Florenzano, F; Bentivoglio, M

    2000-09-04

    In the adult rat brain mast cells reside selectively in the thalamus. We investigated thalamic mast cells stained by acidic toluidine blue or pinacyanol, and with histamine immunocytochemistry, focusing on their state of activity revealed by degranulation. Mast cells exhibited perivascular prevalence and high quantitative variability, between cases and in different sections, with no asymmetry or topographical selectivity in thalamic nuclei. Pinacyanol, alone or with erythrosine, stained mast cells with higher sensitivity than toluidine blue. However, toluidine blue was highly predictive of pinacyanol staining and provided the best resolution of mast cell cytoplasmic features. Histamine immunocytochemistry labeled 61% of pinacyanol-stained mast cells. Intensely toluidine blue-stained granulated cells, as well as cells exhibiting different degrees of degranulation that paralleled lighter staining, were observed. The response of thalamic mast cells to intracerebroventricular administration of nerve growth factor (NGF) and control cytochrome-c injections was evaluated after 2, 24, and 72 hours. No obvious changes in mast cell number or distribution were found after treatment, but massive degranulation was frequently observed after NGF administration. Significant decrease of staining intensity of mast cells, supporting enhanced degranulation, was documented in NGF-treated animals by quantitative image analysis. Ultrastructural features of mast cell degranulation, with granule coalescence and matrix dissolution, were detected in untreated and NGF-treated cases. The findings point out that mast cells are active in the thalamus in basal conditions and that NGF has the potential to elicit long-lasting degranulation of thalamic mast cells in vivo, exerting a direct effect and/or priming these cells to react to endogenous stimuli.

  15. Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy

    Directory of Open Access Journals (Sweden)

    Jeffrey J. Tan

    2017-01-01

    Full Text Available Intravitreal bevacizumab (Avastin use in preterm infants with retinopathy of prematurity is associated with severe neurological disabilities, suggesting vascular leakage. We examined the hypothesis that intermittent hypoxia (IH potentiates intravitreal Avastin leakage. Neonatal rats at birth were exposed to IH from birth (P0–P14. At P14, the time of eye opening in rats, a single dose of Avastin (0.125 mg was injected intravitreally into the left eye. Animals were placed in room air (RA until P23 or P45 for recovery (IHR. Hyperoxia-exposed and RA littermates served as oxygen controls, and equivalent volume saline served as the placebo controls. At P23 and P45 ocular angiogenesis, retinal pathology and ocular and systemic biomarkers of angiogenesis were examined. Retinal flatmounts showed poor peripheral vascularization in Avastin-treated and fellow eyes at P23, with numerous punctate hemorrhages and dilated, tortuous vessels with anastomoses at P45 in the rats exposed to IH. These adverse effects were associated with robust increases in systemic VEGF and in both treated and untreated fellow eyes. Histological analysis showed severe damage in the inner plexiform and inner nuclear layers. Exposure of IH/IHR-induced injured retinal microvasculature to anti-VEGF substances can result in vascular leakage and adverse effects in the developing neonate.

  16. Quantitative evaluation of reduction of plaque-like hard exudates in diabetic macular edema after intravitreal triamcinolone injection.

    Science.gov (United States)

    Cekiç, Osman; Bardak, Yavuz; Tiğ, U Sahin; Yildizoğlu, Uzeyir; Bardak, Handan

    2008-04-01

    To describe a new method of quantifying the amount of plaque-like hard exudates after intravitreal triamcinolone acetonide injection in diabetic macular edema. This study included 22 eyes of 14 patients (mean age, 63 years) with chronic diabetic macular edema and plaque-like hard exudates. The patients were injected with a single dose of 4 mg intravitreal triamcinolone acetonide. The optic disc size as relative size unit was taken to quantify the hard exudates: Total areas of exudates and the optic nerve head were computed from fundus pictures with a digital analysis program on magnified images. The former was divided by the latter, and the results were expressed as a percentage value. The ratio was used to track improvements in a given eye over 6 months. Average ratio of hard exudates to optic nerve head area reduced to 81% of its initial value at 1 month (P=0.007), to 54% at 3 months (Pexudates to optic disc area of diabetic plaque-like hard exudates following 4 mg intravitreal triamcinolone.

  17. Ganglion Cell Complex Evaluation in Exudative Age-Related Macular Degeneration after Repeated Intravitreal Injections of Ranibizumab

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    Andrea Perdicchi

    2015-01-01

    Full Text Available Purpose. To detect the effects of intravitreal ranibizumab injections on GCC in patients with wet AMD. Methods. 32 wet AMD eyes were selected and submitted at three ranibizumab injections. RTVue-OCT GCC and MM5 protocol were performed before treatment and twenty days after each injection. Results. At baseline mean GCC thickness was 93.9 ± 18.5 μm. Twenty days after each intravitreal injection it was, respectively, 85.8 ± 10.1, 86.5 ± 9.3, and 91.1 ± 11.5 μm, without statistical significance. A significant improvement in visual acuity (P = 0.031 and a reduction of mean foveal (P = 0.001 and macular thickness (P = 0.001 were observed. Conclusion. The clinical results confirm therapeutic efficacy of intravitreal injections of ranibizumab in wet AMD. A contemporary not statistically significant reduction of GCC thickness suggests that the loading phase of ranibizumab does not have any toxic effects on ganglion cell complex.

  18. Intravitreal tPA Injection and Pneumatic Displacement for Submacular Hemorrhage in a 10-Year-Old Child

    Directory of Open Access Journals (Sweden)

    Takayuki Tsuyama

    2016-01-01

    Full Text Available Background. Submacular hemorrhage can occur after blunt trauma to the eye. Intravitreal tissue plasminogen activator (tPA and gas injection are often used for treatment and are effective for submacular hemorrhage caused by age-related macular degeneration. This report describes the clinical outcome in a child with submacular hemorrhage caused by traumatic choroidal rupture who underwent successful intravitreal tPA injection and pneumatic displacement. Case Presentation. A 10-year-old boy developed sudden decrease of vision and a central scotoma in his right eye after trauma. Submacular hemorrhage was found in the eye. Visual acuity was 20/70 OD. Tissue plasminogen activator (12.5 μg in 0.05 mL and 0.3 mL of pure sulfur hexafluoride were injected into the vitreous cavity under general anesthesia. After surgery, the patient was instructed to maintain a prone position. Displacement of the submacular hemorrhage from the fovea revealed a choroidal rupture, presumed to be the cause of the hemorrhage. After 4 months of follow-up, visual acuity was restored and final visual acuity is 20/16. Conclusion. Intravitreal tPA and gas injection can be an effective treatment for children with submacular hemorrhage.

  19. Short-term effects of intravitreal dexamethasone implant (OZURDEX® on choroidal thickness in patients with naive branch retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Hasan Basri Arifoglu

    Full Text Available ABSTRACT Purpose: The objective of this study was to evaluate subfoveal choroidal thickness (SFCT using enhanced depth imaging optical coherence tomography (EDI-OCT in patients with naïve branch retinal vein occlusion (BRVO before and after intravitreal dexamethasone implant (Ozurdex® injection. Methods: Thirty-nine patients with unilateral BRVO and 35 healthy subjects were included in this prospective study. Choroidal thickness was evaluated by EDI-OCT at baseline and 1 month after dexamethasone implant. Results: The mean SFCT measured in 39 patients with BRVO was 299.41 ± 55.86 µm, significantly greater than that in contralateral eyes (283.76 ± 57.44 µm; p=0.009 and control eyes (276.14 ± 39.06 µm; p=0.044. The mean SFCT after the treatment was 279.64 ± 50.96 µm, significantly thinner than that before intravitreal dexamethasone therapy (p=0.004. Conclusions: SFCT in treatment-naive BRVO eyes was significantly greater than that in contralateral eyes and healthy eyes and decreased significantly after intravitreal dexamethasone implantation.

  20. Administrating Solr

    CERN Document Server

    Mohan, Surendra

    2013-01-01

    A fast-paced, example-based guide to learning how to administrate, monitor, and optimize Apache Solr.""Administrating Solr"" is for developers and Solr administrators who have a basic knowledge of Solr and who are looking for ways to keep their Solr server healthy and well maintained. A basic working knowledge of Apache Lucene is recommended, but this is not mandatory.

  1. Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick

    Science.gov (United States)

    Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank

    2012-01-01

    Purpose Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Methods Chicks were treated with either +7 D, −7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-AktThr308, and anti-phospho-Erk1/2(Thr202/Tyr204) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Results Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens–treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor

  2. Effects of intravitreal injection of netrin-1 in retinal neovascularization of streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Yu Y

    2015-12-01

    Full Text Available Yao Yu,1,2,* Jing Zou,3,* Yun Han,4 Luowa Quyang,4 Hui He,4 Peihong Hu,2 Yi Shao,2 Ping Tu11Nanchang Key Laboratory of Diabetes, Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Jiangxi, People’s Republic of China; 3Department of Ophthalmology, Xiangya Hospital, Central South University, Hunan, People’s Republic of China; 4Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, Fujian, People’s Republic of China*These authors have contributed equally to this workBackground: In a previous study, we confirmed that netrin-1 acts as an antiangiogenic factor by inhibiting alkali burn-induced corneal neovascularization in rats. Here, we continue working on the role of netrin-1 in retinal neovascularization.Methods: Using an in vitro angiogenesis assay, we detected the effects of netrin-1 on human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion at concentrations of 0.1 µg/mL or 5 µg/mL. We intravitreally injected 0.1 µg/mL or 5 µg/mL netrin-1 into streptozotocin-induced rats to assess retinal neovascularization using retinal electrophysiology and electroretinography, enzyme-linked immunosorbent assay, fundus fluoresce in angiography, measurement of inner blood retinal barrier, retinal hematoxylin-eosin staining, and retinal flat-mount fluorescence assays.Results: Human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion were upregulated by netrin-1 at a concentration of 0.1 µg/mL (P<0.05, while 5 µg/mL netrin-1 had an opposite effect (P<0.05 in our in vitro angiogenesis assay. Retinal electrophysiology testing revealed that intravitreal injection of netrin-1 affected the amplitude of a- and b

  3. Administrative Circulars

    CERN Multimedia

    Département des Ressources humaines

    2004-01-01

    Administrative Circular N° 2 (Rev. 2) - May 2004 Guidelines and procedures concerning recruitment and probation period of staff members This circular has been revised. It cancels and replaces Administrative Circular N° 2 (Rev. 1) - March 2000. Administrative Circular N° 9 (Rev. 3) - May 2004 Staff members contracts This circular has been revised. It cancels and replaces Administrative Circular N° 9 (Rev. 2) - March 2000. Administrative Circular N° 26 (Rev. 4) - May 2004 Procedure governing the career evolution of staff members This circular has also been revised. It Administrative Circulars Administrative Circular N° 26 (Rev. 3) - December 2001 and brings up to date the French version (Rev. 4) published on the HR Department Web site in January 2004. Operational Circular N° 7 - May 2004 Work from home This circular has been drawn up. Operational Circular N° 8 - May 2004 Dealing with alcohol-related problems...

  4. Intravitreal ranibizumab for symptomatic drusenoid pigment epithelial detachment without choroidal neovascularization in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Roberto Gallego-Pinazo

    2011-02-01

    Full Text Available Roberto Gallego-Pinazo1,2, Ana Marina Suelves-Cogollos1, Ester Francés-Muñoz1, J María Millán2,3, J Fernando Arevalo4, J Luis Mullor5, Manuel Díaz-Llopis1,2,61Department of Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain; 3Department of Genetics, Hospital Universitario La Fe, Valencia, Spain; 4Retina and Vitreous Service, Clínica Oftalmológica Centro Caracas, Caracas, Venezuela; 5Unit of Experimental Ophthalmology, Fundación para la Investigación del Hospital Universitario La Fe, Valencia, Spain; 6University of Valencia, Faculty of Medicine, Valencia, SpainBackground: The aim of our study was to evaluate the functional and anatomic outcomes of intravitreal ranibizumab for the treatment of symptomatic drusenoid pigment epithelial detachment without choroidal neovascularization in age-related macular degeneration.Methods: This was a prospective, single-center, uncontrolled, interventional pilot study. Six consecutive eyes (six patients with drusenoid pigment epithelial detachment with a visual acuity of 20/63 to 20/100 and no evidence of choroidal neovascularization in age-related macular degeneration participated. Patients were given at least one intravitreal ranibizumab injection and were followed for a mean of 66.67 ± 10.3 weeks. Main outcome measures included best-corrected visual acuity (BCVA measured by Early Treatment Diabetic Retinopathy Study charts and optical coherence tomography, and central macular thickness measured by optical coherence tomography.Results: The mean number of intravitreal ranibizumab injections was 3.0 at the end of follow-up. Regarding BCVA and optical coherence tomography, 33.3% of eyes gained between 19 and 21 letters of BCVA, with a median decrease in central macular thickness of 21 µm. There was a statistically significant difference between baseline and final BCVA (P = 0.046. There was a positive

  5. Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ba J

    2015-09-01

    Full Text Available Jun Ba,1,2,* Run-Sheng Peng,2,* Ding Xu,1 Yan-Hong Li,1 Hui Shi,1,3 Qianyi Wang,1 Jing Yu11Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, 2Department of Cardiac Surgery, Institute of Cardiovascular Diseases of Fudan University, Affiliated Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*Co-first authors of this workAims: Age-related macular degeneration (AMD is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD.Methods: A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA, retinal thickness, and lesion size were evaluated.Results: Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR group and the intravitreal bevacizumab group (standard mean difference =-0.14, 95% confidence interval [CI] =-0.23 to -0.05. No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN can raise VA by 1.97 letters (weighted mean difference =1.97, 95% CI =0.14–3.794. Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference =2.74, 95% CI =0.26–5.21.Conclusion: The superiority remains unclear between IVR and

  6. EFFICACY AND FREQUENCY OF INTRAVITREAL AFLIBERCEPT VERSUS BEVACIZUMAB FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

    Science.gov (United States)

    Lotfy, Ayman; Solaiman, Kamal A M; Abdelrahman, Ayman; Samir, Ahmed

    2017-08-01

    To compare the safety, efficacy, and frequency of intravitreal injection of aflibercept and bevacizumab for treatment of macular edema secondary to central retinal vein occlusion. Prospective, comparative, randomized, interventional study. Eyes with macular edema secondary to central retinal vein occlusion were randomized between two groups according to the intravitreal injection used. Group A included eyes treated with intravitreal aflibercept, and Group B included eyes treated with intravitreal bevacizumab injections. The inclusion criteria were macular edema secondary to central retinal vein occlusion and follow-up duration of at least 12 months after the first injection. Exclusion criteria were macular ischemia, associated diabetes, hypertensive or renal retinopathy, other retinal disease, and previous anti-vascular endothelial growth factor injection. The main outcome measures are central foveal thickness, best-corrected visual acuity, time intervals between injections, improved retinal nonperfusion, and any reported complication. Group A included 39 patients with a mean age of 57.4 ± 8.2 years. Group B included 40 eyes with a mean age of 56.5 ± 9.1 years. Twelve months after the first injection, central foveal thickness significantly improved from 475.45 ± 71.05 m to 259.11 ± 20.67 m in Group A and from 460.22 ± 89.38 m to 264.29 ± 32.05 m in Group B; best-corrected visual acuity significantly improved from 0.81 ± 0.16 logarithm of the minimum angle of resolution (20/125) to 0.34 ± 0.14 logarithm of the minimum angle of resolution (20/40) in Group A and from 0.73 ± 0.15 logarithm of the minimum angle of resolution (20/100) to 0.33 ± 0.17 logarithm of the minimum angle of resolution (20/40) in Group B; the mean number of injections was 3.72 ± 2.93 in Group A and was 5.44 ± 2.85 in Group B (P Retinal nonperfusion improved in 9/12 eyes in Group A and in 3/8 eyes in Group B (P central retinal vein occlusion without significant complications. However

  7. Sustained-release dexamethasone intravitreal implant in juvenile idiopathic arthritis-related uveitis.

    Science.gov (United States)

    Pichi, Francesco; Nucci, Paolo; Baynes, Kimberly; Lowder, Careen Y; Srivastava, Sunil K

    2017-02-01

    The purpose of this study is to review the results of treatment of juvenile idiopathic arthritis-related uveitis with the use of intravitreal dexamethasone implant. Sixteen eyes with Juvenile idiopathic arthritis (JIA)-associated uveitis received intravitreal dexamethasone implant to treat recalcitrant anterior segment inflammation (43.7 %), chronic macular edema (6.2 %), or a combination of both (50 %). One month after injection, mean visual acuity had improvement to 39.6 ± 11 ETDRS letters (p < 0.001). Mean AC cells measure at 1 month was 0.79 and 0.75 at 3 months. One month after injection, there was a significant reduction of central retinal thickness (CRT) to 342.4 ± 79.3 µm (p < 0.01). One month after the second implant, 11 eyes (91.6 %) achieved improved activity of the anterior uveitis, and mean best-corrected visual acuity improved to 44.6 ± 8.1 ETDRS letters (p < 0.01). At 1 month after the second injection, 4/5 eyes had resolution of macular edema with CRT of 250.4 ± 13.7 µm (p < 0.01). Of the 16 eyes, 12 eyes received a second injection at mean of 7.5 ± 3.1 months after the first treatment, and 5 eyes received a third Ozurdex injection on average 7 ± 4.6 months after the second injection. Of the 16 eyes, five eyes were pseudophakic prior to injection. Of the remaining 11 eyes, 8 (73 %) developed worsening posterior subcapsular cataract at a mean of 7.3 ± 1.2 months after the first injection. After the first injection, only one eye required topical antiglaucoma therapy with maximum pressure of 25 mmHg. In patients with recalcitrant JIA-associated active uveitis, injection of sustained-release dexamethasone can achieve control of anterior inflammation and resolution of macular edema.

  8. Effects of three consecutive monthly intravitreal injection of ranibizumab for polypoidal choroidal vasculopathy in Korea

    Institute of Scientific and Technical Information of China (English)

    Young; Gun; Park; Seungbum; Kang; Young; Jung; Roh

    2015-01-01

    AIM: To evaluate the efficacy and safety of three consecutive monthly injections of intravitreal ranibizumab for the treatment of polypoidal choroidal vasculopathy(PCV) in Korea.METHODS: A retrospective chart review of 25 patients(27 eyes) with PCV was conducted. Patients received three initial monthly intravitreal injections(0.5 mg) of ranibizumab and were monitored monthly for 12 mo from January 2010 to October 2011. Reinjection of ranibizumab after three initial monthly loading was administered on an as-needed basis, guided by the optical coherence tomography(OCT), fluorescein angiography(FA) and indocyanine green angiography(ICGA). The main outcomes were the changes of the mean best corrected Snellen visual acuity(VA), central macular thickness(CMT) by OCT, the changes of polyps and branching vascular network by FA and ICGA, and total number of injections received by patients during the 12 mo.RESULTS: The mean best corrected Snellen visual acuities at baseline, 1, 3, 6 and 12 mo after primary injection were 0.77 ±0.59, 0.76 ±0.53, 0.70 ±0.47, 0.63 ±0.43,0.61 ±0.43, 0.62 ±0.42 log MAR, respectively, and showed significant improvement at 3, 6, 12mo(P =0.003, P =0.002,P =0.018, Wilcoxon signed-rank test). The mean CMT at baseline, 1, 2, 3, 6, and 12 mo was 312.41 ±66.38 μm,244.59 ±71.47 μm, 232.32 ±69.41 μm, 226.69 ±69.03 μm,228.62 ±37.07 μm, 227.59 ±51.01 μm respectively, and showed significant reduction(all P <0.001, Wilcoxon signed-rank test). Polypoidal lesions resolved on ICGA in 3 eyes(11.1%) and a branching vascular network remained in all 24 eyes(88.9%). A total of 106 injections were given in the 12-month period, which equaled to a mean of 3.92(range, 3-6) times. Sixteen of the 27 treatedeyes had additional 1.56 ±0.91 injections. The others(11eyes) had just 3 consecutive injections.CONCLUSION: An initial loading dose of three monthly ranibizumab injections is a safe and effective method in treating PCV, with visual and anatomical

  9. The effect of intravitreal anti-VEGF agents on peripheral wound healing in a rabbit model

    Directory of Open Access Journals (Sweden)

    Christoforidis J

    2012-01-01

    Full Text Available John Christoforidis1, Robert Ricketts1, Cedric Pratt1, Jordan Pierce1, Scott Bean1, Michael Wells1, Xiaoli Zhang2, Krista La Perle31College of Medicine, 2Center for Biostatistics, 3College of Veterinary Medicine, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal pegaptanib, bevacizumab, and ranibizumab on blood-vessel formation during cutaneous wound healing in a rabbit model and to compare this effect to placebo controls.Methods: Forty New Zealand albino rabbits underwent full thickness cutaneous wounds using 6-mm dermatologic punch biopsies. The rabbits were assigned to four groups of ten, each receiving intravitreal injections of pegaptanib, bevacizumab, ranibizumab, or no injection (untreated controls. Five rabbits from each group underwent wound harvesting on day 7 and five from each group on day 14. The skin samples were stained with hematoxylin and eosin (HE, Masson's trichrome (MT, and CD34 for vascular endothelial cells. Semiquantitative evaluation of HE- and MT-stained slides was performed by one pathologist. Quantitative assessment of mean neovascularization (MNV scores was obtained from five contiguous biopsy margin 400× fields of CD34-stained sections by four independent observers.Results: Week 1 MNV scores in CD-34 stained sections were: untreated controls: 11.51 ± 4.36; bevacizumab: 7.41 ± 2.82 (P = 0.013; ranibizumab: 8.71 ± 4.08 (P = 0.071; and pegaptanib: 10.15 ± 5.59 (P = 0.378. Week 2 MNV data were: untreated controls: 6.14 ± 2.25; bevacizumab: 7.25 ± 2.75 (P = 0.471; ranibizumab: 4.53 ± 3.12 (P = 0.297; and, pegaptanib: 6.35 ± 3.09 (P = 0.892. Interobserver variability using intraclass correlation coefficient was 0.961.Conclusions: At week 1, all three anti-VEGF agents had suppressed MNV scores compared to controls. Although not statistically significant, there was an inhibitory trend, particularly with bevacizumab and ranibizumab. These effects were diminished at 2 weeks

  10. Effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections

    Institute of Scientific and Technical Information of China (English)

    Mustafa; Atas; Burhan; Baskan; Ayse; zkse; Fatma; Mutlu; Sarιgüzel; Süleyman; Demircan; Emine; Pangal

    2014-01-01

    AIM:To evaluate the effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections.METHODS:Seventy-two eyes of 36 patients [36 eyes in control group, 36 eyes in intravitreal injection(IVI) group]were enrolled in the study. All the eyes had at least one IVI and had diabetic macular edema(DME) or age-related macular degeneration(ARMD). Moxifloxacin was prescribed to all the patients four times a day for five days following injection. Conjunctival cultures were obtained from the lower fornix via standardized technique with every possible effort made to minimize contamination from the lids, lashes, or skin. Before the application of any ophthalmic medication, conjunctival cultures were obtained from both eyes using sterile cotton culture. An automated microbiology system was used to identify the growing bacteria and determine antibiotic sensitivity.RESULTS:The bacterial cultures were isolated from 72 eyes of 36 patients, sixteen of whom patients(44.4%)were male and twenty(55.6%) were female. Average age was 68.4 ±9.0(range 50-86). The average number of injections before taking cultures was 3.1+1.0. Forty-eight(66.7%) of 72 eyes had at least one significant organism.There was no bacterial growth in 8(20.5%) of IVI eyes and in 16(44.4%) of control eyes(P =0.03). Of the bacteria isolated from culture, 53.8% of coagulase negative staphylococci(CoNS) in IVI eyes and 47.2%CoNS in control eyes. This difference between IVI eyes and control eyes about bacteria isolated from culture was not statistically significant(P =0.2). Eleven of 25 bacteria(44.0%) isolated from IVI eyes and 11(57.9%) of 19 bacteria isolated from control eyes were resistant to oxacillin. The difference in frequency of moxifloxacine resistance between two groups was not statistically significant(12.0% in IVI eyes and 21.1% in control eyes)(P =0.44). There were no cases of resistance to vancomycin, teicoplanin and linezolid

  11. Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

    Directory of Open Access Journals (Sweden)

    Yan Lu

    2014-02-01

    Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

  12. Administrative Reform

    DEFF Research Database (Denmark)

    Plum, Maja

    Through the example of a Danish reform of educational plans in early childhood education, the paper critically addresses administrative educational reforms promoting accountability, visibility and documentation. Drawing on Foucaultian perspectives, the relation between knowledge and governing...... of administrative technology, tracing how the humanistic values of education embed and are embedded within ‘the professional nursery teacher' as an object and subject of administrative practice. Rather than undermining the humanistic potential of education, it is argued that the technology of accounting...

  13. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes.

    Science.gov (United States)

    Chang-Lin, Joan-En; Burke, James A; Peng, Qing; Lin, Ton; Orilla, Werhner C; Ghosn, Corine R; Zhang, Kai-Ming; Kuppermann, Baruch D; Robinson, Michael R; Whitcup, Scott M; Welty, Devin F

    2011-06-28

    To evaluate dexamethasone pharmacokinetics after implantation of a sustained-release dexamethasone (DEX) intravitreal implant in nonvitrectomized and vitrectomized eyes. The right eyes of 25 rabbits underwent vitrectomy; contralateral eyes served as nonvitrectomy controls. The 0.7-mg DEX implant was injected into both eyes, and drug concentrations were determined in the vitreous humor and retina for 31 days (on days 2, 8, 15, 22, and 31). DEX was present in nonvitrectomized and vitrectomized eyes for at least 31 days. There were no statistically significant differences in DEX concentration between nonvitrectomized and vitrectomized eyes at any time point (P > 0.05). The maximum concentration of DEX in nonvitrectomized versus vitrectomized eyes for vitreous humor was 791 ng/mL (day 22) versus 731 ng/mL (day 22), respectively, and for retina it was 4110 ng/mL (day 15) versus 3670 ng/mL (day 22), respectively. Mean absorption (AUC(0-tlast)) of dexamethasone in nonvitrectomized and vitrectomized eyes was not different for both the vitreous humor (13,600 vs. 15,000 ng/day/mL; P = 0.73) and retina (67,600 vs. 50,200 ng/day/mL; P = 0.47). The vitreoretinal pharmacokinetic profiles were similar between nonvitrectomized and vitrectomized eyes. These observations are consistent with clinical findings of the DEX implant in patients who have undergone vitrectomy and should reduce concerns about the use of the DEX implant in eyes that have undergone vitrectomy.

  14. Letter to the editor: dexamethasone intravitreal implant in the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Hall J

    2015-11-01

    Full Text Available John Hall Alimera Sciences Ltd., Aldershot, Hampshire, UK I read “Dexamethasone intravitreal implant in the treatment of diabetic macular edema” published July 2015 by Dugel et al.1This article is very interesting in terms of providing an outline of the role of inflammation in the pathogenesis of diabetic macular edema and explaining the value of corticosteroids in the treatment of diabetic macular edema. However, I would like to draw your attention to the data presented for ILUVIEN® (fluocinolone acetonide; FAc in Table 2, which has been presented incorrectly and does not reflect the approved product and dose in Europe. ILUVIEN is indicated in Europe for the treatment of vision impairment associated with chronic diabetic macular edema, considered insufficiently responsive to available therapies2 and is approved in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, and the United Kingdom. ILUVIEN was launched in the United Kingdom in April 2013, Germany in May 2013, and Portugal in January 2015.3View original paper by Dugel et al.

  15. Development of a murine ocular posterior segment explant culture for the study of intravitreous vector delivery.

    Science.gov (United States)

    Denk, Nora; Misra, Vikram; Sandmeyer, Lynne S; Bauer, Bianca B; Singh, Jaswant; Forsyth, George W; Grahn, Bruce H

    2015-01-01

    The objective of this study was to develop a murine retinal/choroidal/scleral explant culture system to facilitate the intravitreous delivery of vectors. Posterior segment explants from adult mice of 2 different age groups (4 wk and 15 wk) were cultured in serum-free medium for variable time periods. Tissue viability was assessed by gross morphology, cell survival quantification, activated caspase-3 expression, and immunohistochemistry. To model ocular gene therapy, explants were exposed to varying transducing units of a lentiviral vector expressing the gene for green fluorescent protein for 48 h. Explant retinal cells remained viable for approximately 1 wk, although the ganglion cell layer developed apoptosis between 4 and 7 d. Following vector infusion into the posterior segment cups, viral transduction was noted in multiple retinal layers in both age groups. An age of donor mouse influence was noted and older mice did not transduce as well as younger mice. This explant offers an easily managed posterior segment ocular culture with minimum disturbance of the tissue, and may be useful for investigating methods of enhancing retinal gene therapy under controlled conditions.

  16. Waiting time reduction in intravitreal clinics by optimization of appointment scheduling: balancing demand and supply.

    Science.gov (United States)

    Ugarte, Marta

    2015-01-01

    This study was designed guided by the Model for Improvement framework to reduce waiting times and visit duration in the intravitreal therapy clinic, while improving patient and staff experience. In our aim to provide good quality, patient-centred care and constantly improve, we optimised the appointment profile and patient flow. We involved a multidisciplinary team (one consultant, junior doctors, staff nurses, technicians, and receptionist), as well as patients and relatives, to try to understand the main delays in the clinic. Process mapping, a fishbone diagram, run charts, together with feedback from patients and staff, provided an insight on the possible roots of the delays experienced by our patients. The results of the inquiry led us to take actions focused on optimising appointment scheduling. After implementing the new scheduling profile (with a gap in the middle of the session), various cycles of plan-do-study-act and a comparative, qualitative study by interviewing 10 patients demonstrated that the waiting times decreased, and patients and staff experience improved.

  17. Choroidal thickness changes after intravitreal ranibizumab and photodynamic therapy in recurrent polypoidal choroidal vasculopathy.

    Science.gov (United States)

    Maruko, Ichiro; Iida, Tomohiro; Oyamada, Hiroshi; Sugano, Yukinori; Ojima, Akira; Sekiryu, Tetsuju

    2013-09-01

    To evaluate subfoveal choroidal thickness changes in cases with recurrent polypoidal choroidal vasculopathy (PCV) after combination therapy with intravitreal ranibizumab and photodynamic therapy (PDT). Retrospective observational case series study. We measured subfoveal choroidal thickness in PCV using optical coherence tomography (OCT) before and after PDT. In recurrent cases, the choroidal thickness was measured at the time of the recurrence. In nonrecurrent cases, choroidal thickness was measured 1 year after PDT. Combination therapy was performed in 27 eyes (27 patients). Polypoidal lesions regressed within 3 months after initial treatment in all eyes. Retreatment was needed in 10 of 27 eyes (37.0%) after more than 3 months of follow-up. In recurrent cases, subfoveal choroid decreased from 188 μm at baseline to 157 μm 3 months after PDT (P choroidal thickness increased to 179 μm with recurrence (P = .54 compared to baseline; average, 8.0 months). In nonrecurrent cases, subfoveal choroid decreased from 257 μm at baseline to 210 μm 3 months after PDT and 212 μm 1 year after PDT (P choroidal thickness in PCV at the time of recurrence returned to the baseline level after choroidal thinning as a result of PDT treatment. Choroidal thickness changes after PDT examined using OCT may reflect disease activity in PCV. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Two Cases of Acute Abdomen after an Intravitreal Injection of Bevacizumab

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    Yasutaka Onoda

    2015-03-01

    Full Text Available We report on a patient with ischemic colitis and another with paralytic ileus, both of whom experienced an acute abdomen after intravitreal injection of bevacizumab (IVB. Case 1 was a 78-year-old woman. Her medical history included surgery for colon carcinoma 10 years earlier. The patient developed acute severe abdominal pain and nausea the day after IVB for retinal vein occlusion with macular edema, and massive lower gastrointestinal bleeding occurred. Ischemic colitis was diagnosed. Case 2 was a 64-year-old man who presented with neovascular glaucoma with proliferative diabetic retinopathy. We performed vitreous surgery on the 9th day after IVB, and we reperformed IVB at the end of the vitreous surgery. On the first postoperative day, severe abdominal distension, vomiting and abdominal pain were observed, and paralytic ileus was diagnosed. It is possible that gastrointestinal disorders are induced after IVB, depending on the patient's background, including for example severe diabetes or a history of surgery for gastrointestinal cancer. Thus, ophthalmologists should apply alternative therapies instead of IVB to patients with severe diabetes mellitus or a history of gastrointestinal cancer.

  19. Two Cases of Acute Abdomen after an Intravitreal Injection of Bevacizumab

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    Onoda, Yasutaka; Shiba, Tomoaki; Hori, Yuichi; Maeno, Takatoshi; Takahashi, Mao

    2015-01-01

    We report on a patient with ischemic colitis and another with paralytic ileus, both of whom experienced an acute abdomen after intravitreal injection of bevacizumab (IVB). Case 1 was a 78-year-old woman. Her medical history included surgery for colon carcinoma 10 years earlier. The patient developed acute severe abdominal pain and nausea the day after IVB for retinal vein occlusion with macular edema, and massive lower gastrointestinal bleeding occurred. Ischemic colitis was diagnosed. Case 2 was a 64-year-old man who presented with neovascular glaucoma with proliferative diabetic retinopathy. We performed vitreous surgery on the 9th day after IVB, and we reperformed IVB at the end of the vitreous surgery. On the first postoperative day, severe abdominal distension, vomiting and abdominal pain were observed, and paralytic ileus was diagnosed. It is possible that gastrointestinal disorders are induced after IVB, depending on the patient's background, including for example severe diabetes or a history of surgery for gastrointestinal cancer. Thus, ophthalmologists should apply alternative therapies instead of IVB to patients with severe diabetes mellitus or a history of gastrointestinal cancer. PMID:25960733

  20. Catalytic nanoceria are preferentially retained in the rat retina and are not cytotoxic after intravitreal injection.

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    Lily L Wong

    Full Text Available Cerium oxide nanoparticles (nanoceria possess catalytic and regenerative radical scavenging activities. The ability of nanoceria to maintain cellular redox balance makes them ideal candidates for treatment of retinal diseases whose development is tightly associated with oxidative damage. We have demonstrated that our stable water-dispersed nanoceria delay photoreceptor cell degeneration in rodent models and prevent pathological retinal neovascularization in vldlr mutant mice. The objectives of the current study were to determine the temporal and spatial distributions of nanoceria after a single intravitreal injection, and to determine if nanoceria had any toxic effects in healthy rat retinas. Using inductively-coupled plasma mass spectrometry (ICP-MS, we discovered that nanoceria were rapidly taken up by the retina and were preferentially retained in this tissue even after 120 days. We also did not observe any acute or long-term negative effects of nanoceria on retinal function or cytoarchitecture even after this long-term exposure. Because nanoceria are effective at low dosages, nontoxic and are retained in the retina for extended periods, we conclude that nanoceria are promising ophthalmic therapeutics for treating retinal diseases known to involve oxidative stress in their pathogeneses.

  1. Intravitreal Injection of Bevacizumab for Retinopathy of Prematurity in an Infant with Peters Anomaly

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    Tsuyoshi Minami

    2014-10-01

    Full Text Available Purpose: To report our findings in an infant with Peters anomaly type II whose retinopathy of prematurity (ROP was treated with an anti-VEGF agent and surgeries. Case Report: A male infant weighing 548 g was born prematurely at 23 weeks and 1 day with corneal opacity and shallow anterior chambers in both eyes. At the postmenstrual age of 35 weeks and 3 days, the infant was tentatively diagnosed with stage 3 ROP because of a dilated tunica vasculosa lentis and ultrasonographic findings. The boy was treated with bilateral intravitreal injections of bevacizumab (IVB because laser photocoagulation of the retina could not be performed due to the corneal opacity. The retina in the right eye detached 3 times, namely 5 days, 16 days, and 7 months after the IVB; encircling the scleral buckle and a vitrectomy with endolaser photocoagulation were therefore required. In his left eye, the retina was reattached after the initial IVB, and no additional treatment was required. ROP was not reactivated in both eyes until the last examination at the age of 2 years and 6 months. Conclusions: Our results showed that IVB is a useful treatment for ROP in patients with Peters anomaly. However, a retinal detachment can be a complication after IVB. The optimal timing of IVB for ROP in infants with hazy media needs to be determined.

  2. Expression Profile of Intravitreous Cytokines, Chemokines and Growth Factors in Patients with Fuchs Heterochromic Iridocyclitis

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    Kaori Suzuki

    2010-05-01

    Full Text Available Purpose: To report the postoperative courses of 2 patients with Fuchs heterochromic iridocyclitis (FHI and the concentrations of various cytokines, chemokines and growth factors in vitreous fluid samples to obtain insights into pathobiochemical aspects. Subjects: The patients were a 27- and a 47-year-old woman. Phacoemulsification and aspiration, intraocular lens (IOL implantation, and pars plana vitrectomy were performed to treat their cataracts and vitreous opacities. During their early postoperative periods, inflammatory cells precipitated on the IOL and intraocular pressure was increased in both patients. Methods: At the time of surgery, undiluted vitreous fluid specimens were collected. The concentrations of multiple cytokines, chemokines and growth factors were measured by a bead array immunodetection system. Results: The levels of interleukin-1ra, -5, -6, -8, -10 and -13, interferon-inducible 10-kDa protein, monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, and regulated upon activation, normal T-cell expressed and secreted (RANTES were significantly elevated in vitreous fluid in both patients. Conclusion: Although the postoperative course was generally favorable in patients with FHI, steroid instillation was necessary for a few months postoperatively, as precipitates easily formed on the IOL surface and elevated intraocular pressure. The profiles of intravitreal concentrations of cytokines, chemokines and growth factors may characterize postoperative inflammatory reactions.

  3. Intravitreal transplantation of human umbilical cord blood stem cells protects rats from traumatic optic neuropathy.

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    Bing Jiang

    Full Text Available OBJECTIVES: To treat traumatic optic neuropathy (TON with transplantation of human umbilical cord blood stem cells (hUCBSC and explore how transplanted stem cells participate in the neuron repairing process. METHODS: A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP. Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR. RESULTS: After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression. CONCLUSION: Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.

  4. Long-Term Management of Complications of Retinal Artery Macroaneurysms with Intravitreal Aflibercept Injection

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    Kishore, Kamal

    2016-01-01

    Purpose To report the 1-year follow-up results of intravitreal aflibercept injection (IAI) for the management of complications of retinal artery macroaneurysms (RAM). Methods A retrospective, noncomparative, interventional case series of 4 eyes of 4 patients (all female, aged 68–91 years, 3 treatment naive) treated with IAI 2 mg for complications of RAM [macular edema (ME) 2, submacular hemorrhage (SMH) 1, and vitreous hemorrhage (VH) 1] was conducted. Baseline parameters consisted of complete ocular examination, medical history, best-corrected Snellen VA, fundus photography, IVFA and SD OCT, unless precluded by VH (1). All patients completed ≥1 year follow-up. Results Baseline VA was hand motions in the eye with SMH (31 mm2 area and 1,478 μm thickness); 20/40 and 20/100 with ME (CST 390 and 337 μm, respectively), and 20/200 in the eye with VH. At 1 month, both patients with ME showed resolution of ME with CST Thrombosis of RAM was noted in all eyes and hairpin-like remodeling of artery in one. No eye required repeat injection or laser. Conclusion ME and VH from RAM were effectively treated with IAI. However, the eye with thick SMH had poor visual outcome despite thrombosis of RAM. Single IAI provided effective therapy for complications of RAM with excellent anatomical and visual results in each eye, except one with thick SMH, and merits further study.

  5. Posterior Pole Sparing Laser Photocoagulation Combined with Intravitreal Bevacizumab Injection in Posterior Retinopathy of Prematurity

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    Rebecca Kim

    2014-01-01

    Full Text Available Purpose. To report the results of the posterior pole sparing laser photocoagulation combined with intravitreal bevacizumab injection (IVB in retinopathy of prematurity (ROP. Methods. A retrospective chart review of premature babies with ROP, all of whom received laser photocoagulation with IVB. Eleven eyes of 6 infants with advanced zone I ROP underwent laser ablation sparing posterior pole with concurrent IVB. The results were compared with those of full-laser treatment combined with IVB to 8 eyes of 5 infants with advanced ROP without involvement of the posterior pole. Results. The posterior pole sparing laser with IVB was performed with zone I, stage 3+ ROP at the mean postmenstrual age of 36 weeks and 5 days. The plus sign decreased significantly at postoperative day 1, the neovascular proliferation regressed by postoperative week 1, and the normal vascularization started at postoperative day 32 on the average. Two months after treatment, vascularization of the spared avascular area was completed. There was no macular dragging, tractional retinal detachment, foveal destruction by laser scars, or any other adverse event. No significant anatomical differences were identified from those of full-laser ablation combined with IVB. Conclusions. Posterior pole sparing laser with IVB can give favorable results without destruction of posterior pole retina.

  6. Antibacterial properties of 2% lidocaine and reduced rate of endophthalmitis after intravitreal injection.

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    Tustin, Aaron; Kim, Stephen J; Chomsky, Amy; Hubbard, G Baker; Sheng, Jinsong

    2014-05-01

    To determine whether the application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce rates of endophthalmitis after intravitreal (IVT) injection. We performed in vitro experiments to determine the antibacterial properties of 2% lidocaine/0.1% methylparaben (lidocaine) against causative organisms of endophthalmitis. Isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans from patients with endophthalmitis were incubated with or without lidocaine. Aliquots (100 µL) were plated on Mueller-Hinton (S. aureus and S. epidermidis) or blood agar plates (S. viridans) at 0, 10, 30, 120, and 240 minutes, and colonies were counted after 24 hours. A retrospective review of 15,042 IVT injections was performed from January 2004 to February 2011 to determine the rate of endophthalmitis with or without application of subconjunctival lidocaine for anesthesia. Lidocaine demonstrated rapid bactericidal effects against all 3 organisms. After 10 minutes of exposure, there was approximately a 90% (P 2% (P lidocaine and 8 cases of endophthalmitis of 8,189 (0.1%) IVT injections performed with other methods of anesthesia (P = 0.03). Application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce the incidence of endophthalmitis after IVT injection.

  7. Intravitreal Triamcinolone for Acute Branch Retinal Vein Occlusion: a Randomized Clinical Trial

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    Alireza Ramezani

    2011-01-01

    Full Text Available Purpose: To evaluate the therapeutic effect of intravitreal triamcinolone (IVT injection for recent branch retinal vein occlusion (BRVO. Methods: In a randomized controlled clinical trial, 30 phakic eyes with recent (less than 10 weeks′ duration BRVO were assigned to two groups. The treatment group (16 eyes received 4 mg IVT and the control group (14 eyes received subconjunctival sham injections. Changes in visual acuity (VA were the main outcome measure. Results: VA and central macular thickness (CMT changes were not significantly different between the study groups at any time point. Within group analysis showed significant VA improvement from baseline in the IVT group up to three months (P 0.05. Significant reduction in CMT was noticed only in the treatment group (‑172 ± 202 μm, P = 0.029 and at 4 months. Ocular hypertension occurred in 4 (25% and 2 (14.3% eyes in the IVT and control groups, respectively. Conclusion: A single IVT injection had a non-significant beneficial effect on VA and CMT in acute BRVO as compared to the natural history of the condition. The 3-month deferred treatment protocol advocated by the Branch Vein Occlusion Study Group may be a safer option than IVT injection considering its potential side effects.

  8. Clivorine, an otonecine pyrrolizidine alkaloid from Ligularia species, impairs neuronal differentiation via NGF-induced signaling pathway in cultured PC12 cells.

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    Xiong, Aizhen; Yan, Artemis Lu; Bi, Cathy W C; Lam, Kelly Y C; Chan, Gallant K L; Lau, Kitty K M; Dong, Tina T X; Lin, Huangquan; Yang, Li; Wang, Zhengtao; Tsim, Karl W K

    2016-08-15

    Pyrrolizidine alkaloids (PAs) are commonly found in many plants including those used in medical therapeutics. The hepatotoxicities of PAs have been demonstrated both in vivo and in vitro; however, the neurotoxicities of PAs are rarely mentioned. In this study, we aimed to investigate in vitro neurotoxicities of clivorine, one of the PAs found in various Ligularia species, in cultured PC12 cells. PC12 cell line was employed to first elucidate the neurotoxicity and the underlying mechanism of clivorine, including cell viability and morphology change, neuronal differentiation marker and signaling pathway. PC12 cells were challenged with series concentrations of clivorine and/or nerve growth factor (NGF). The cell lysates were collected for MTT assay, trypan blue staining, immunocytofluorescent staining, qRT-PCR and western blotting. Clivorine inhibited cell proliferation and neuronal differentiation evidenced by MTT assay and dose-dependently reducing neurite outgrowth, respectively. In addition, clivorine decreased the level of mRNAs encoding for neuronal differentiation markers, e.g. neurofilaments and TrkA (NGF receptor). Furthermore, clivorine reduced the NGF-induced the phosphorylations of TrkA, protein kinase B and cAMP response element-binding protein in cultured PC12 cells. Taken together, our results suggest that clivorine might possess neurotoxicities in PC12 cells via down-regulating the NGF/TrkA/Akt signaling pathway. PAs not only damage the liver, but also possess neurotoxicities, which could possibly result in brain disorders, such as depression. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. Bone marrow mesenchymal stem cells attenuate 2,5-hexanedione-induced neuronal apoptosis through a NGF/AKT-dependent pathway

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    Wang, Qingshan; Sun, Guohua; Gao, Chenxue; Feng, Lina; Zhang, Yan; Hao, Jie; Zuo, Enjun; Zhang, Cong; Li, Shuangyue; Piao, Fengyuan

    2016-01-01

    Growing evidence suggests that the increased neuronal apoptosis is involved in n-hexane-induced neuropathy. We have recently reported that bone marrow-mesenchymal stem cells-derived conditioned medium (BMSC-CM) attenuated 2,5-hexanedione (HD, the active metabolite of n-hexane)-induced apoptosis in PC12 cells. Here, we explored the anti-apoptotic efficacy of BMSC in vivo. HD-treated rats received BMSC by tail vein injection 5 weeks after HD intoxication. We found that in grafted rats, BMSC significantly attenuated HD-induced neuronal apoptosis in the spinal cord, which was associated with elevation of nerve growth factor (NGF). Neutralization of NGF in BMSC-CM blocked the protection against HD-induced apoptosis in VSC4.1 cells, suggesting that NGF is essential for BMSC-afforded anti-apoptosis. Mechanistically, we found that the decreased activation of Akt induced by HD was significantly recovered in the spinal cord by BMSC and in VSC4.1 cells by BMSC-CM in a TrkA-dependent manner, leading to dissociation of Bad/Bcl-xL complex in mitochondria and release of anti-apoptotic Bcl-xL. The importance of Akt was further corroborated by showing the reduced anti-apoptotic potency of BMSC in HD-intoxicated VSC4.1 cells in the presence of Akt inhibitor, MK-2206. Thus, our findings show that BMSC attenuated HD-induced neuronal apoptosis in vivo through a NGF/Akt-dependent manner, providing a novel solution against n-hexane-induced neurotoxicity. PMID:27703213

  10. Effect of NGF, BDNF, bFGF, aFGF and cell density on NPY expression in cultured rat dorsal root ganglion neurones.

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    Kerekes, N; Landry, M; Lundmark, K; Hökfelt, T

    2000-07-01

    The effect of neurotrophic factors on neuropeptide Y (NPY) expression was studied in adult rat dispersed dorsal root ganglion (DRG) cultures. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), acidic fibroblast growth factor (aFGF) or basic FGF was included in the culture medium during incubation for 72 h. In untreated cultures, around 18% of all neurones (visualized by antibodies to PGP 9.5) expressed NPY-like immunoreactivity (LI). In contrast, in vivo uninjured neurones do not contain detectable levels of NPY-LI. In the immunohistochemical analysis aFGF increased the percentage of NPY-immunoreactive (-IR) neurones 1.8-fold, while NGF, BDNF or bFGF had no significant effect on NPY expression. When the effect of these growth factors was monitored with non-radioactive in situ hybridization, both aFGF and bFGF caused a significant increase (2.25- and 1.8-fold, respectively), whereas, again, NGF and BDNF had no effect. The results also showed an effect of cell density on NPY expression, whereby fewer neurones expressed NPY in high than in low density cultures. This difference was seen in untreated as well as growth factor-treated cultures. The present results support the hypothesis that DRG neurones in culture are in an axotomized state, since they express NPY to about the same extent as axotomized DRG neurones in vivo. Surprisingly, two growth factors of the FGF family enhance NPY expression in DRG neurones, which is in apparent contrast to a published in vivo study [Ji, R.-R., Zhang, Q., Pettersson, R.F., Hökfelt, T., 1996. aFGF, bFGF and NGF differentially regulate neuropeptide expression in dorsal root ganglia after axotomy and induce autotomy. Reg. Pept. 66, 179-189.]. Finally, NPY expression was also influenced by cell density.

  11. Secreted herpes simplex virus-2 glycoprotein G modifies NGF-TrkA signaling to attract free nerve endings to the site of infection.

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    Jorge Rubén Cabrera

    2015-01-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 and HSV-2 are highly prevalent viruses that cause a variety of diseases, from cold sores to encephalitis. Both viruses establish latency in peripheral neurons but the molecular mechanisms facilitating the infection of neurons are not fully understood. Using surface plasmon resonance and crosslinking assays, we show that glycoprotein G (gG from HSV-2, known to modulate immune mediators (chemokines, also interacts with neurotrophic factors, with high affinity. In our experimental model, HSV-2 secreted gG (SgG2 increases nerve growth factor (NGF-dependent axonal growth of sympathetic neurons ex vivo, and modifies tropomyosin related kinase (TrkA-mediated signaling. SgG2 alters TrkA recruitment to lipid rafts and decreases TrkA internalization. We could show, with microfluidic devices, that SgG2 reduced NGF-induced TrkA retrograde transport. In vivo, both HSV-2 infection and SgG2 expression in mouse hindpaw epidermis enhance axonal growth modifying the termination zone of the NGF-dependent peptidergic free nerve endings. This constitutes, to our knowledge, the discovery of the first viral protein that modulates neurotrophins, an activity that may facilitate HSV-2 infection of neurons. This dual function of the chemokine-binding protein SgG2 uncovers a novel strategy developed by HSV-2 to modulate factors from both the immune and nervous systems.

  12. Administrative Ecology

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    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  13. Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

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    Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

    2016-11-08

    Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

  14. Association of TrkA and APP Is Promoted by NGF and Reduced by Cell Death-Promoting Agents.

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    Canu, Nadia; Pagano, Ilaria; La Rosa, Luca Rosario; Pellegrino, Marsha; Ciotti, Maria Teresa; Mercanti, Delio; Moretti, Fabiola; Sposato, Valentina; Triaca, Viviana; Petrella, Carla; Maruyama, Ichiro N; Levi, Andrea; Calissano, Pietro

    2017-01-01

    The amyloid precursor protein (APP) interacts with the tropomyosin receptor kinase A (TrkA) in normal rat, mouse, and human brain tissue but not in Alzheimer's disease (AD) brain tissue. However, it has not been reported whether the two proteins interact directly, and if so, which domains are involved. Clarifying these points will increase our understanding of the role and regulation of the TrkA/APP interaction in normal brain functioning as well as in AD. Here we addressed these questions using bimolecular fluorescence complementation (BiFC) and the proximity ligation assay (PLA). We demonstrated that exogenously expressed APP and TrkA associate through their juxtamembrane/transmembrane domains, to form a complex that localizes mainly to the plasma membrane, endoplasmic reticulum (ER) and Golgi. Formation of the complex was inhibited by p75NTR, ShcC and Mint-2. Importantly, we demonstrated that the association between endogenous APP and TrkA in primary septal neurons were modified by NGF, or by drugs that either inhibit ER-to-Golgi transport or perturb microtubules and microfilaments. Interestingly, several agents that induce cell death [amyloid β (Aβ)-peptide, staurosporine and rapamycin], albeit via different mechanisms, all caused dissociation of APP/TrkA complexes and increased production of C-terminal fragment (β-CTF) APP fragment. These findings open new perspectives for investigating the interplay between these proteins during neurodegeneration and AD.

  15. Association of TrkA and APP Is Promoted by NGF and Reduced by Cell Death-Promoting Agents

    Science.gov (United States)

    Canu, Nadia; Pagano, Ilaria; La Rosa, Luca Rosario; Pellegrino, Marsha; Ciotti, Maria Teresa; Mercanti, Delio; Moretti, Fabiola; Sposato, Valentina; Triaca, Viviana; Petrella, Carla; Maruyama, Ichiro N.; Levi, Andrea; Calissano, Pietro

    2017-01-01

    The amyloid precursor protein (APP) interacts with the tropomyosin receptor kinase A (TrkA) in normal rat, mouse, and human brain tissue but not in Alzheimer’s disease (AD) brain tissue. However, it has not been reported whether the two proteins interact directly, and if so, which domains are involved. Clarifying these points will increase our understanding of the role and regulation of the TrkA/APP interaction in normal brain functioning as well as in AD. Here we addressed these questions using bimolecular fluorescence complementation (BiFC) and the proximity ligation assay (PLA). We demonstrated that exogenously expressed APP and TrkA associate through their juxtamembrane/transmembrane domains, to form a complex that localizes mainly to the plasma membrane, endoplasmic reticulum (ER) and Golgi. Formation of the complex was inhibited by p75NTR, ShcC and Mint-2. Importantly, we demonstrated that the association between endogenous APP and TrkA in primary septal neurons were modified by NGF, or by drugs that either inhibit ER-to-Golgi transport or perturb microtubules and microfilaments. Interestingly, several agents that induce cell death [amyloid β (Aβ)-peptide, staurosporine and rapamycin], albeit via different mechanisms, all caused dissociation of APP/TrkA complexes and increased production of C-terminal fragment (β-CTF) APP fragment. These findings open new perspectives for investigating the interplay between these proteins during neurodegeneration and AD. PMID:28197073

  16. Comparison of P2X and TRPV1 receptors in ganglia or primary culture of trigeminal neurons and their modulation by NGF or serotonin

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    Giniatullin Rashid

    2006-03-01

    Full Text Available Abstract Background Cultured sensory neurons are a common experimental model to elucidate the molecular mechanisms of pain transduction typically involving activation of ATP-sensitive P2X or capsaicin-sensitive TRPV1 receptors. This applies also to trigeminal ganglion neurons that convey pain inputs from head tissues. Little is, however, known about the plasticity of these receptors on trigeminal neurons in culture, grown without adding the neurotrophin NGF which per se is a powerful algogen. The characteristics of such receptors after short-term culture were compared with those of ganglia. Furthermore, their modulation by chronically-applied serotonin or NGF was investigated. Results Rat or mouse neurons in culture mainly belonged to small and medium diameter neurons as observed in sections of trigeminal ganglia. Real time RT-PCR, Western blot analysis and immunocytochemistry showed upregulation of P2X3 and TRPV1 receptors after 1–4 days in culture (together with their more frequent co-localization, while P2X2 ones were unchanged. TRPV1 immunoreactivity was, however, lower in mouse ganglia and cultures. Intracellular Ca2+ imaging and whole-cell patch clamping showed functional P2X and TRPV1 receptors. Neurons exhibited a range of responses to the P2X agonist α, β-methylene-adenosine-5'-triphosphate indicating the presence of homomeric P2X3 receptors (selectively antagonized by A-317491 and heteromeric P2X2/3 receptors. The latter were observed in 16 % mouse neurons only. Despite upregulation of receptors in culture, neurons retained the potential for further enhancement of P2X3 receptors by 24 h NGF treatment. At this time point TRPV1 receptors had lost the facilitation observed after acute NGF application. Conversely, chronically-applied serotonin selectively upregulated TRPV1 receptors rather than P2X3 receptors. Conclusion Comparing ganglia and cultures offered the advantage of understanding early adaptive changes of nociception

  17. Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells.

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    Mazzio, E; Georges, B; McTier, O; Soliman, Karam F A

    2015-10-01

    Post-mitotic central nervous system (CNS) neurons have limited capacity for regeneration, creating a challenge in the development of effective therapeutics for spinal cord injury or neurodegenerative diseases. Furthermore, therapeutic use of human neurotrophic agents such as nerve growth factor (NGF) are limited due to hampered transport across the blood brain barrier (BBB) and a large number of peripheral side effects (e.g. neuro-inflammatory pain/tissue degeneration etc.). Therefore, there is a continued need for discovery of small molecule NGF mimetics that can penetrate the BBB and initiate CNS neuronal outgrowth/regeneration. In the current study, we conduct an exploratory high-through-put (HTP) screening of 1144 predominantly natural/herb products (947 natural herbs/plants/spices, 29 polyphenolics and 168 synthetic drugs) for ability to induce neurite outgrowth in PC12 dopaminergic cells grown on rat tail collagen, over 7 days. The data indicate a remarkably rare event-low hit ratio with only 1/1144 tested substances (Momordica cochinchinensis seed extract (MCS). To quantify the neurotrophic effects of MCS, 36 images (n = 6) (average of 340 cells per image), were numerically assessed for neurite length, neurite count/cell and min/max neurite length in microns (µm) using Image J software. The data show neurite elongation from 0.07 ± 0.02 µm (controls) to 5.5 ± 0.62 µm (NGF 0.5 μg/mL) and 3.39 ± 0.45 µm (138 μg/mL) in MCS, where the average maximum length per group extended from 3.58 ± 0.42 µm (controls) to 41.93 ± 3.14 µm (NGF) and 40.20 ± 2.72 µm (MCS). Imaging analysis using immunocytochemistry (ICC) confirmed that NGF and MCS had similar influence on 3-D orientation/expression of 160/200 kD neurofilament, tubulin and F-actin. These latent changes were associated with early rise in phosphorylated extracellular signal-regulated kinase (ERK) p-Erk1 (T202/Y204)/p-Erk2 (T185/Y187) at 60 min with mild changes in pAKT peaking at 5 min, and no

  18. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study.

    Science.gov (United States)

    Brown, David M; Heier, Jeffrey S; Clark, W Lloyd; Boyer, David S; Vitti, Robert; Berliner, Alyson J; Zeitz, Oliver; Sandbrink, Rupert; Zhu, Xiaoping; Haller, Julia A

    2013-03-01

    To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO). Randomized controlled trial. This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n = 115) or sham (n = 74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4 + PRN and sham + IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52. At week 24, 56.1% of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3% of sham patients (P < .001). At week 52, 55.3% of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1% of sham + IAI PRN patients (P < .001). At week 52, IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN (P < .001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure. Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Evaluation of efficacy dexamethasone intravitreal implant compared to treatment with anti-VEGF in the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Elena Pacella

    2014-12-01

    Full Text Available Objective: The study compares the effectiveness of an intravitreal slow-release dexamethasone implant respect to an intravitreal injection of a anti-VEGF, ranibizumab, in the treatment of diabetic macular edema (DME. Design: we used a non randomized retrospective study to compare the effectiveness of two treatment approaches to DME Subjects: 50 patients were investigated, 30 of whom underwent injections of ranibizumab and 20 of whom underwent dexamethasone implantation. Methods: When patients were injected with the anti-VEGF ranibizumab, they were monitored every three months. Dexamethasone implant was administered only once in 6 months, different to ranibizumab which was administered monthly . Main Outcome Measures: these were carried out by measuring the improvements in ETDRS (visual acuity scores and CMT (central macular thickness after one month, three months, and six months (T1, T3, T6. intraocular pressure were performed. Results: Data evidenced that the slow-release dexamethasone implant is more efficacious than the intravitreal injection of the anti-VEGF, ranibizumab, in terms of improvement of visual acuity and central macular thickness. Dexamethasone implant at T3 produced an improvement of visual acuity which was significantly better respect to injections of ranibizumab, with a mean ETDRS gain of nearly 8,5 letters, compared to only 4 letters gained in the case of ranibizumab injected patients. This significance, however, is lost by T6, (p=0.516, where those treated with dexamethasone had lost 6 of the eight letters gained, while those with ranibizumab had lost 4 letters. As such, the overall gain at the T6 checkpoint was only 2.5 letters for dexamethasone implant and 2 for ranibizumab. Conclusion: The study highlighted a better initial efficacy of the dexamethasone implant due to its superior performance at 3 and 6 month evaluation points.

  20. Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT

    Directory of Open Access Journals (Sweden)

    Vinicius F. Kniggendorf

    2016-06-01

    Full Text Available ABSTRACT Purpose: To evaluate choroidal thickness (CT using spectral domain optical coherence tomography (SD-OCT imaging at baseline and 6 months after intravitreal anti-vascular endothelial growth factor (anti-VEGF treatment in patients with diabetic macular edema (DME. Methods: A retrospective chart review was performed to identify patients with DME who underwent intravitreal injection of anti-VEGF (bevacizumab or ranibizumab in a pro re nata (PRN regimen. Subfoveal choroidal thickness was compared between values obtained at baseline and at 6-month follow-up visits. Results: Thirty-nine eyes (15 females, 24 males from 39 patients were enrolled (mean age, 62.43 ± 8.7 years; range, 44-79 years. Twenty-three and 16 eyes were treated with ranibizumab and bevacizumab respectively. The mean number of anti-VEGF injections was 2.28 ± 1.27 (range, 1-5. Mean nasal, subfoveal, and temporal choroidal thickness (CT measurements at baseline were 234.10 ± 8.63 µm, 246.89 ± 8.94 µm, and 238.12 ± 8.20 µm, respectively, and those at 6 months post-treatment were 210.46 ± 8.00 µm, 215.66 ± 8.29 µm, and 212.43 ± 8.14 µm, respectively. Significant differences in CT were observed between baseline and the 6-month follow-up at all measured points (p=0.0327. Conclusions: Over a 6-month period, the use of intravitreal anti-VEGF was associated with significant thinning of the choroid in patients with DME. The clinical significance of a thinner choroid in DME is currently unknown; however, it may contribute to long-term adverse effects on choroidal and retinal function, representing an area requiring future investigation.

  1. Health-related quality of life, visual function and treatment satisfaction following intravitreal dexamethasone implant for diabetic macular edema

    Science.gov (United States)

    Ramu, Jayashree; Chatziralli, Irini; Yang, Yit; Menon, Geeta; Bailey, Clare; Eckstein, Michael; Hykin, Phil; Sivaprasad, Sobha

    2017-01-01

    Purpose The aim of this study was to explore and describe quantitatively patient-reported outcome measures (PROMs), ie, health-related quality of life (QoL), visual function and treatment satisfaction, in patients with diabetic macular edema (DME) receiving two different regimens of Ozurdex (intravitreal dexamethasone implant). Methods In this multicenter, prospective study, 100 patients with center-involving refractory DME were randomized 1:1 to either five monthly fixed dosing or optical coherence tomography (OCT)-guided pro re nata (PRN) regimen of dexamethasone intravitreal implant therapy. The primary outcome was the difference between arms in change in PROMs and health-related QoL from baseline to 12 months, as measured by the Retinopathy-Dependent Quality of Life (RetDQoL) questionnaire, Visual Function Questionnaire-25 (VFQ-25) and Retinopathy Treatment Satisfaction Questionnaire (RetTSQ). Results There was no statistically significant difference in the RetDQoL score and VFQ-25 score at month 12 compared to those at baseline, whereas the total mean RetTSQ score increased significantly at the exit visit. The two treatment arms did not differ significantly regarding the change in PROMs and health-related QoL questionnaires. Logistic regression analysis showed that visual acuity (VA) of ≥55 letters, central foveal thickness statistically significant improvement in treatment satisfaction, as measured by RetTSQ, in patients with DME treated with dexamethasone intravitreal implant, independent of the dose regimen, namely, fixed or PRN. However, it should be noted that the clinically meaningful change could not be assessed accurately, since no thresholds for clinically meaningful change currently exist for the RetTSQ. On the other hand, there was no significant change in health-related QoL, as measured using VFQ-25 and RetDQoL. Factors affecting the patients’ treatment satisfaction were the final VA, the central foveal thickness and the macular volume. PMID

  2. Evaluation of RNFL thickness and serum cytokine levels after retinal photocoagulation combined with intravitreous Conbercept injection treatment of diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Luo Na

    2016-01-01

    Objective:To evaluate the effect of retinal photocoagulation combined with intravitreous Conbercept injection in RNFL thickness, serum cytokine levels and other aspects of diabetic retinopathy.Methods:A total of 92 patients with diabetic retinopathy (126 eyes) who received inpatient treatment in our hospital from December, 2013 to December 2015 were included in the study and divided into observation group 46 cases (62 eyes) and control group 46 cases (64 eyes) according to random number table, control group received retinal photocoagulation therapy alone, observation group received retinal photocoagulation combined with intravitreous Conbercept injection treatment, and then differences in RNFL thickness, hemodynamic indexes, serum levels of cytokines and others were compared between two groups after treatment.Results: Average RNFL thickness of inner optic disc top, bottom, bitamporal and nasal ring area as well as the average full-cycle 360° RNFL thickness of observation group after treatment was less than those of control group; PSV and EDV values of CRA were higher than those of control group while RI value was lower than that of control group, and PSV, EDV and RI values of CRV were lower than those of control group; serumβ2-GPⅠ, Hcy, VEGF and SDF-1 levels were lower than those of control group while C-peptide and APN levels were higher than those of control group.Conclusion: Retinal photocoagulation combined with intravitreous Conbercept injection can significantly reduce the RNFL thickness of the patients with diabetic retinopathy and optimize the retinal hemodynamic status, and helps to improve patients’ overall conditions.

  3. Clinical, anatomical, and electrophysiological assessments of the central retina following intravitreal bevacizumab for macular edema secondary to retinal vein occlusion.

    Science.gov (United States)

    Loukianou, Eleni; Brouzas, Dimitrios; Chatzistefanou, Klio; Koutsandrea, Chrysanthi

    2016-02-01

    The purpose of this study is to evaluate the long-term visual, anatomical and electrophysiological outcomes of repeated intravitreal injections of bevacizumab for macular edema due to retinal vein occlusion (RVO) and investigate any possible toxic effects on the central fovea. This is a prospective, noncomparative, interventional case series. Thirty-three eyes of 33 patients with macular edema secondary to RVO were treated with 1.25 mg/0.05 ml intravitreal bevacizumab. Nine patients had nonischemic central retinal vein occlusion (CRVO) and 24 patients had branch retinal vein occlusion (BRVO). The main outcome measures were best-corrected visual acuity, central retinal thickness (CRT), and multifocal electroretinography (mfERG) responses changes at baseline, 1 month after the third injection and at the end of the 2-year long follow-up period. Patients with CRVO had mean best-corrected Snellen visual acuity of 0.10 at baseline, which improved significantly to 0.31 after 2 years (P = 0. 028).The mean CRT at presentation was 756.28 μm and reduced significantly to 439.14 μm after 2 years (P = 0.05). Patients with BRVO had mean best-corrected Snellen visual acuity of 0.19 at baseline, which improved significantly to 0.40 after 2 years (P central 10° (ring1, ring2) showed statistically significant differences on P1 parameters in terms of response density and implicit time after 2 years in both CRVO and BRVO patients. Repeated intravitreal bevacizumab injections for macular edema due to either CRVO or BRVO resulted in long-term improvement of visual acuity, a reduction in CRT and statistically significant changes in the mfERG responses with nondemonstrable toxic effects on the central fovea.

  4. Evaluation of the effectiveness and safety of glucocorticoids intravitreal implant therapy in macular edema due to retinal vein occlusion.

    Science.gov (United States)

    Michalska-Małecka, Katarzyna; Gaborek, Aneta; Nowak, Mariusz; Halat, Tomasz; Pawłowska, Mariola; Śpiewak, Dorota

    2016-01-01

    The purpose of this study was to evaluate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and functions in eyes with macular edema (ME) secondary to retinal vein occlusion. Efficacy outcomes of the treatment were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Safety outcomes were intraocular pressure and cornea endothelial cell density. The study was conducted by the prospective analysis on 36 patients (17 women and 19 men) aged 28-77 years (the average age was 58±15 years) treated with the injection of dexamethasone implant because of the persistent ME at the Department of Ophthalmology and Ophthalmology Outpatient Clinic of the University Centre of Ophthalmology and Oncology in Katowice. The studied group included 16 patients with central retinal vein occlusion (16 eyes), and 20 patients with branch retinal vein occlusion (20 eyes). We found a significant increase of BCVA after first, second, and third month of treatment. Six months after the treatment, BCVA decreased, although not significantly compared with the value obtained in the third month. Two months after the intravitreal implantation of dexamethasone delivery system, CRT was 338±163 μm and was significantly lower compared with pretreatment value. Between third and sixth month after the treatment, we found insignificant increase of CRT compared with thickness observed in second month. Two months after the treatment, we found an increase in intraocular pressure in 36% of cases and a further decrease during the final visit 6 months after the treatment. During the treatment, there were no significant differences in endothelial cell density in branch retinal vein occlusion and central retinal vein occlusion. We found the intravitreal dexamethasone implant to be safe, well tolerated, and likely to lead to fast morphological and functional improvement of the macula and visual rehabilitation in patients with ME due to retinal vein occlusion.

  5. Effect of prophylactic timolol 0.1% gel on intraocular pressure after an intravitreal injection of ranibizumab: a randomized study

    OpenAIRE

    Pece, Alfredo; Allegrini, Davide; Montesano, Giovanni; Dimastrogiovanni, Andrea Fabio

    2016-01-01

    Purpose The purpose of this study is to make a prospective evaluation of the effect of timolol 0.1% eye gel on short-term intraocular pressure (IOP) after an intravitreal injection (IVI) of ranibizumab. Participants and methods One hundred and fifty eyes of 150 IVI-naïve patients with macular edema caused by various pathological conditions (age-related macular degeneration, central or branch retinal vein occlusion, and diabetic retinopathy) were scheduled to undergo an IVI of ranibizumab (0.5...

  6. Combination therapy of low-fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane in choroidal osteoma

    Directory of Open Access Journals (Sweden)

    Rodney J Morris

    2011-01-01

    Full Text Available Choroidal osteoma is an unusual form of intraocular calcification seen in otherwise healthy eyes. It is a benign idiopathic osseous tumor of the choroid, typically seen in young females. Choroidal neovascular membrane (CNVM is a complication seen in one-third of these patients and carries a poor visual outcome. We report a case of a 25-year-old hyperthyroid female with choroidal osteoma and subfoveal CNVM in her left eye which was successfully treated using low-fluence photodynamic therapy (PDT with verteporfin followed by a single injection of intravitreal ranibizumab.

  7. Evaluation of the effectiveness and safety of glucocorticoids intravitreal implant therapy in macular edema due to retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Michalska-Małecka K

    2016-05-01

    Full Text Available Katarzyna Michalska-Małecka,1,2 Aneta Gaborek,2 Mariusz Nowak,3 Tomasz Halat,4 Mariola Pawłowska,2 Dorota Śpiewak2 1Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, 2University Center of Ophthalmology and Oncology, Independent Public Clinical Hospital, Medical University of Silesia, Katowice, 3Pathophysiology Division, Department of Pathophysiology and Endocrinology, Medical University of Silesia, School of Medicine with Division of Density, Zabrze, 4Education and Medical Simulation Center, Medical University of Silesia, Katowice, Poland Abstract: The purpose of this study was to evaluate the impact of intravitreal dexamethasone implant (Ozurdex on macular morphology and functions in eyes with macular edema (ME secondary to retinal vein occlusion. Efficacy outcomes of the treatment were best-corrected visual acuity (BCVA and central retinal thickness (CRT. Safety outcomes were intraocular pressure and cornea endothelial cell density. The study was conducted by the prospective analysis on 36 patients (17 women and 19 men aged 28–77 years (the average age was 58±15 years treated with the injection of dexamethasone implant because of the persistent ME at the Department of Ophthalmology and Ophthalmology Outpatient Clinic of the University Centre of Ophthalmology and Oncology in Katowice. The studied group included 16 patients with central retinal vein occlusion (16 eyes, and 20 patients with branch retinal vein occlusion (20 eyes. We found a significant increase of BCVA after first, second, and third month of treatment. Six months after the treatment, BCVA decreased, although not significantly compared with the value obtained in the third month. Two months after the intravitreal implantation of dexamethasone delivery system, CRT was 338±163 µm and was significantly lower compared with pretreatment value. Between third and sixth month after the treatment, we found insignificant increase of

  8. Offentlig administration

    DEFF Research Database (Denmark)

    Nielsen, Elof Nellemann; Rehr, Preben René

    En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer.......En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer....

  9. Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization.

    Science.gov (United States)

    Traversi, Claudio; Nuti, Elisabetta; Marigliani, Davide; Cevenini, Gabriele; Balestrazzi, Angelo; Martone, Gianluca; Caporossi, Tomaso; Tosi, Gian Marco

    2015-04-01

    To evaluate the long-term efficacy of bevacizumab in the treatment of choroidal neovascularization (CNV) secondary to pathological myopia. In this retrospective single-center non-comparative study the medical records of 29 eyes from 29 patients with naïve CNV secondary to high myopia and at least 42 months of follow up were reviewed. All eyes received a loading dose of one intravitreal injection per month for two consecutive months and were retreated on an as-needed basis during the course of follow up. The main outcome measures were post-treatment ETDRS best-corrected visual acuity (BCVA) and visual stabilization over time. Stepwise linear regression analysis was performed to identify prognostic factors for visual acuity gain and final visual acuity outcome at 42 months. At 42 months of follow-up bevacizumab was associated with the maintenance of significant benefits in visual acuity compared to baseline. No adverse ocular or systemic effects from treatment were encountered. No statistically significant correlations were found between BCVA change and any of the quantitative variables. However, when final BCVA was taken as a dependent variable and CNV size and pre-treatment VA were included as predictors, a bivariate model was identified by stepwise regression which gave a 75 % of explained variance. Bevacizumab treatment was found to be efficacious in the treatment of myopic CNV, resulting in stable gains in visual acuity lasting at least 42 months, without any adverse ocular or general events. Myopic CNV size was identified as a significant prognostic factor.

  10. Long-Term Management of Complications of Retinal Artery Macroaneurysms with Intravitreal Aflibercept Injection

    Directory of Open Access Journals (Sweden)

    Kamal Kishore

    2016-09-01

    Full Text Available Purpose: To report the 1-year follow-up results of intravitreal aflibercept injection (IAI for the management of complications of retinal artery macroaneurysms (RAM. Methods: A retrospective, noncomparative, interventional case series of 4 eyes of 4 patients (all female, aged 68–91 years, 3 treatment naive treated with IAI 2 mg for complications of RAM [macular edema (ME 2, submacular hemorrhage (SMH 1, and vitreous hemorrhage (VH 1] was conducted. Baseline parameters consisted of complete ocular examination, medical history, best-corrected Snellen VA, fundus photography, IVFA and SD OCT, unless precluded by VH (1. All patients completed ≥1 year follow-up. Results: Baseline VA was hand motions in the eye with SMH (31 mm2 area and 1,478 μm thickness; 20/40 and 20/100 with ME (CST 390 and 337 μm, respectively, and 20/200 in the eye with VH. At 1 month, both patients with ME showed resolution of ME with CST <300 μm with improvement in VA which was maintained through 1 year. VH resolved in one eye at 1 month with no recurrence after 1 year. The eye with SMH developed macular scar and had counting fingers vision at 1 year. Thrombosis of RAM was noted in all eyes and hairpin-like remodeling of artery in one. No eye required repeat injection or laser. Conclusion: ME and VH from RAM were effectively treated with IAI. However, the eye with thick SMH had poor visual outcome despite thrombosis of RAM. Single IAI provided effective therapy for complications of RAM with excellent anatomical and visual results in each eye, except one with thick SMH, and merits further study.

  11. Intravitreal bevacizumab and Ahmed glaucoma valve implantation in patients with neovascular glaucoma

    Institute of Scientific and Technical Information of China (English)

    Hai-Tao; Zhang; Yu-Xin; Yang; Ying-Ying; Xu; Rui-Min; Yang; Bao-Jun; Wang; Jun-Xi; Hu

    2014-01-01

    AIM:To explore the efficacy of preoperative intravitreal bevacizumab(IVB) injection combined with Ahmed glaucoma valve(AGV) implantation in the treatment of neovascular glaucoma(NVG).METHODS:This retrospective study included 35 eyes from 35 patients who underwent preoperative IVB and AGV implantation for treatment of NVG. Findings such as intraocular pressure(IOP) number of anti-glaucoma medications, visual acuity(VA), surgical success rates,and complications were recorded.RESULTS:AfterAGVimplantation,IOPwas18.2±4.0mmHg,15.5±3.3 mm Hg and 9.8±2.6 mm Hg at 6, 12 and 36 mo,significantly decreased compared with pre-IOP(P <0.01).The number of anti-glaucoma medications was 0.9 ±0.5,0.8 ±0.9 and 0.8 ±0.6 at 6, 12 and 36 mo, significantly decreased compared to pre-treatment(P <0.01). At last visit, there were 19 eyes with stable VA, 4 with VA improvement, 12 with diminished VA and 3 with complete loss light perception. There were 7 cases that failed during 3-year fellow up period. Cumulative probabilities of valve survival by Kaplan-Meier analysis were 82.9%,74.1% and 71.0% at 12, 24 and 36 mo, respectively. Cox stepwise regression analysis found that the survival time was significant associated with the pre-visual acuity <2/400(P <0.05). Post-operative complications occurred in 8eyes, of which hyphema presented in 2 eyes, choroidal effusion in 2 eyes.CONCLUSION:The procedure of preoperative IVB andAGV implantation should be one of treatments for NVG because of its safety and effectiveness.

  12. The effect of intravitreal injections on dry eye, and proposed management strategies

    Directory of Open Access Journals (Sweden)

    Laude A

    2017-08-01

    Full Text Available Augustinus Laude,1–3 Jimmy WK Lim,1,2 Vishwanath Srinagesh,4 Louis Tong2,5–7 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 2Singapore Eye Research Institute, 3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 4Krieger Eye Institute, Baltimore, MD, USA; 5Singapore National Eye Centre, 6Duke NUS Medical School, 7Yong Loo Lin School of Medicine, National University of Singapore, Singapore Abstract: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF agents has become a commonly used treatment method for a number of ophthalmic conditions, including age-related macular degeneration. Although anti-VEGF therapy has shown promising results for many patients, there are several aspects of its application that have not been thoroughly investigated. One of these is the development and/or escalation of concurrent dry eye syndrome. Many patients undergoing treatment are already predisposed to dry eye disease due to their age and overall ocular health. As dry eye can have a substantial impact on quality of life, it has become increasingly apparent that the clinical signs and symptoms should be closely monitored and aggressively managed. This will allow for the optimization of patient comfort and visual potential. Here, we discuss the reasons why dry eye may develop during the course of repeated ocular anti-VEGF therapy, highlighting the key concerns about current practices and proposing possible solutions to improve the outcome for the patients. Keywords: age-related macular degeneration, povidone–iodine, toxicity, ocular health, chronic ophthalmic treatment

  13. Intravitreal injection of IGFBP-3 restores normal insulin signaling in diabetic rat retina.

    Directory of Open Access Journals (Sweden)

    Youde Jiang

    Full Text Available Diabetes-induced changes in growth factor binding protein 3 (IGFBP-3 and tumor necrosis factor alpha (TNFα have been linked to decreased insulin receptor signaling in diabetic retinopathy. Our previous studies in retinas of diabetic rats have shown that Compound 49b, a novel β-adrenergic receptor agonist, prevented diabetic changes by increasing IGFBP-3 and decreasing TNFα, thus restoring insulin signaling and protection against diabetic retinopathy. The current study was designed to determine whether boosted expression of IGFBP-3 NB (a non-IGF-1 binding form of IGFBP-3 alone is sufficient to mimic the full actions of Compound 49b in protecting against diabetic retinopathy, as well as testing whether IGFBP-3 NB is linked to a restoration of normal insulin signal transduction. Two months after initiation of streptozotocin-induced diabetes, rats received a single intravitreal injection of IGFBP-3 NB plasmid in the right eye. Four days after injection, electroretinogram (ERG analyses were performed prior to sacrifice. Whole retinal lysates from control, diabetic, diabetic + control plasmid, and diabetic+ IGFBP-3 NB were analyzed for IGFBP-3, TNFα, suppressor of cytokine signaling 3 (SOCS3, and insulin receptor signaling partners using Western blotting or ELISA. Data show that a single intraocular injection of IGFBP-3 NB in diabetic animals significantly reduced TNFα levels, concomitant with reductions in IRS-1Ser307, SOCS3, and pro-apoptotic markers, while restoring insulin receptor phosphorylation and increasing anti-apoptotic marker levels. These cellular changes were linked to restoration of retinal function. Our findings establish IGFBP-3 as a pivotal regulator of the insulin receptor/TNFα pathway and a potential therapeutic target for diabetic retinopathy.

  14. Efficacy of Intravitreal Bevacizumab in Treatment of Proliferative Type 2 Idiopathic Juxtafoveal Telangiectasia

    Directory of Open Access Journals (Sweden)

    Ökkeş Baz

    2017-06-01

    Full Text Available Objectives: To evaluate the effectiveness of intravitreal bevacizumab (IVB in patients with subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia. Materials and Methods: Ten eyes of 10 patients were included in this retrospective study. All cases were treated with IVB (1.25 mg bevacizumab. Visual acuity and slit-lamp anterior and posterior segment examinations were performed at each visit. Central macular thickness (CMT and intraretinal/subretinal fluid were evaluated via spectral domain optical coherence tomography (OCT. Loss of a line in visual acuity chart and presence of fluid on OCT were defined as criteria for repeated treatment. Results: The mean age of patients was 66.0±7.0 years (56-75. The mean follow-up time was 54.7±16.0 month (24-72. The mean BCVA was 0.62±0.35 (0.00-1.00 logMAR at baseline and 0.54±0.35 (0.00-1.00 logMAR at final exam (p=0.03. The mean CMT was 251±25.4 µm at baseline and 239±39.3 µm at final exam (p=0.01. Patients received an average of 1.7±1.0 IVB injections during follow-up. At baseline, all cases had intraretinal/subretinal fluid. There was no fluid at final examination of all cases. Conclusion: IVB treatment may be effective in the treatment of subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.

  15. Intravitreal anti-VEGF therapy for neovascular age-related macular degeneration and the risk of stroke.

    LENUS (Irish Health Repository)

    Cleary, C A

    2011-05-01

    The purpose of this study was to compare the vascular event rate in AMD patients treated with an intravitreal VEGF inhibitor with a historical control group treated with photodynamic therapy. We reviewed medical records of 83 patients treated with intravitreal anti-VEGF for AMD between 2005-2007, and 60 patients treated with PDT between 2001-2004. Mean follow-up in the anti-VEGF group was 40 months versus 95 months in the PDT group. Mean age (76 +\\/- 9 years, versus 74 +\\/- 10 years, p=n.s.) and cardiovascular risk factor profile were similar. Vascular event rates in each group were 2.6 per 100 patient years versus 2.3 per 100 patient years, (p = n.s). Age over 80 years was associated with an increased risk of a vascular event (odds ratio = 1.113, p<0.05). Despite the high prevalence of risk factors in AMD patients, the incidence of vascular events was low and associated with older age rather than therapy received.

  16. A cluster of presumed, noninfectious endophthalmitis after intravitreal injection of bevacizumab: long-term follow-up

    Science.gov (United States)

    Ricci, Federico; Calabrese, Antonio; De Felici, Cecilia; Missiroli, Filippo; Pileri, Marco; Regine, Federico

    2016-01-01

    Purpose To report the outcome of 5 consecutive cases of presumed, noninfectious endopththalmitis following intravitreal injection of bevacizumab (IVB). Methods Ten pre-loaded syringes of bevacizumab (1.25 mg/50 µL) furnished by a compounding pharmacy were injected intravitreally. Treatments were performed in the operating room by the same surgeon on 2 consecutive days. Results Of 10 eyes, 5 showed moderate to severe ocular inflammation within a few days of injection. All patients were treated in the same surgical session. Vitreous tap performed in the patient presenting with the most severe grade of inflammation was negative for bacteria and fungi. At the time of the vitreous biopsy, this patient was injected with vancomycin 1 mg/100 µL in the vitreous cavity. Other eyes with moderate inflammation received topical and systemic antibiotics and topical steroid treatment. Visual acuity returned to pre-endophthalmitis or better levels in all eyes within 1 month. The other 5 patients treated with IVB from the same batch in the other surgical session did not develop inflammation. Conclusions IVB can induce noninfectious endophthalmitis. The use of compounded syringes can explain clustering of the inflammation. We were unable to identify the reasons for the variable grade of inflammation we observed in our patients. PMID:27582674

  17. G-quartet oligonucleotide mediated delivery of proteins into photoreceptors and retinal pigment epithelium via intravitreal injection.

    Science.gov (United States)

    Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2016-04-01

    There is currently no available method to efficiently deliver proteins across the plasma membrane of photoreceptor or retinal pigment epithelium (RPE) cells in vivo. Thus, current clinical application of recombinant proteins in ophthalmology is limited to the use of proteins that perform their biological function extracellularly. The ability to traverse biological membranes would enable the mobilization of a significantly larger number of proteins with previously well characterized properties. Nucleolin is abundantly present on the surface of rapidly dividing cells including cancer cells. Surprisingly, nucleolin is also present on the surface of photoreceptor cell bodies. Here we investigated whether nucleolin can be utilized as a gateway for the delivery of proteins into retinal cells following intravitreal injection. AS1411 is a G-quartet aptamer capable of targeting nucleolin. Subsequent to intravitreal injection, fluorescently labeled AS1411 localized to various retinal cell types including the photoreceptors and RPE. AS1411 linked to streptavidin (a ∼50 kDa protein) via a biotin bridge enabled the uptake of Streptavidin into photoreceptors and RPE. AS1411-Streptavidin conjugate applied topically to the cornea allowed for uptake of the conjugate into the nucleus and cytoplasm of corneal endothelial cells. Clinical relevance of AS1411 as a delivery vehicle was strongly indicated by demonstration of the presence of cell surface nucleolin on the photoreceptors, inner neurons and ganglion cells of human retina. These data support exploration of AS1411 as a means of delivering therapeutic proteins to diseased retina.

  18. Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice

    Science.gov (United States)

    Hu, Zong-Li; Li, Ni; Wei, Xin; Tang, Li; Wang, Ting-Hua; Chen, Xiao-Ming

    2017-01-01

    AIM To assess the neuro-protective effect of bone marrow mesenchymal stem cells (BMSCs) on retinal ganglion cells (RGCs) following optic nerve crush in mice. METHODS C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs (BIM), and GDNF-interference BMSCs (GIM) following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively. RESULTS The density (cell number/mm2) of RGCs was 410.77±56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39±195.97 in the normal control (PBIM (354.07+39.77) and GIM (326.67+33.37) than that without treatment (P<0.05). BMSCs injection improved the internal BDNF expression in retinas. CONCLUSION Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs. PMID:28149774

  19. Improvement of visual acuity based on optical coherence tomography patterns following intravitreal bevacizumab treatment in patients with diabetic macular edema

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    Haider R. Cheema

    2014-04-01

    Full Text Available AIM:To report the visual outcome based on various patterns of optical coherence tomography (OCT morphology in diabetic macular edema (DME, following treatment with anti-VEGF intravitreal bevacizumab (IVB injection.METHODS:Sixty-seven consecutive subjects with centre involving DME underwent intravitreal injection of Bevacizumab (1.25 mg/0.05 mL in this retrospective, comparative, non randomized study. The DME was classified into one of four categories:focal, diffuse, focal cystoid and neurosensory detachment based on OCT. Best corrected visual acuity (BCVA, macular appearance, and OCT findings were used to decide whether the subject should have a repeat injection of intravitreal bevacizumab. Outcome measures were a change in mean BCVA (Snellen converted to logMAR and central macular thickness (CMT in each group during the six month follow-up period.RESULTS:The mean BCVA improved to logMAR 0.23 at final follow-up from a baseline of 0.32 logMAR (P=0.040 in the focal group, logMAR 0.80 at final follow-up from a baseline of 0.82 logMAR (P=0.838 in the diffuse group, worsened to logMAR 0.53 at final follow-up from a baseline of 0.43 logMAR (P=0.276 in the focal cystoid group, and improved to logMAR 0.79 at final follow-up from a baseline of 0.93 logMAR (P=0.490 in the neurosensory detachment group. The mean CMT before treatment were 298.8±25.03 μm in the focal group, 310.8±40.6 μm in the diffuse group, 397.15±31.05 μm in the focal cystoid group and 401.03±75.1 μm in the neurosensory detachment group. A mean of 2.05 (range:1-5 injections in the focal group, 1.32 (range:1-2 in the diffuse group, 2.6 (range:1-6 in the focal cystoid group and 2.6 (range:1-6 in the neurosensory detachment group were performed during the six month follow-up period. Following intravitreal bevacizumab treatment, vision improved, remained unchanged or worsened in 11, 7 and 2 subjects in focal group; 11, 9 and 8 in diffuse group; 0, 2 and 4 in focal cystoid group and 5

  20. 神经生长因子(NGF)在母牛性腺及性腺外生殖器官中的表达研究%Expression of Nerve Growth Factor in Ovary, Oviduct and Uterus in Cattle

    Institute of Scientific and Technical Information of China (English)

    马永和; 李纯锦; 孙永峰; 周虚

    2010-01-01

    本研究旨在探讨神经生长因子(nerve growth factor,NGF)在母牛卵泡期及黄体期子宫、卵巢、输卵管3种组织中的表达情况.采用FQ-PCR方法和Western blotting技术对成年母牛卵泡期及黄体期的子宫、卵巢、输卵管中的NGF mRNA和蛋白质表达进行了检测.结果表明,NGF mRNA和蛋白质在卵泡期和黄体期的子宫、卵巢、输卵管中均有表达,且卵泡期子宫中NGF mRNA表达量显著高于卵泡期卵巢和黄体期输卵管中NGF mRNA表达量(P<0.05),其它组织间无显著差异.

  1. Assessment of effect of intravitreal ranibizumab injection on the ocular blood flow in patients with neovascular age-related macular degeneration

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    V. V. Neroev

    2014-07-01

    Full Text Available Purpose: To evaluate the effect of intravitreal ranibizumab injection on the ocular blood flow in patients with neovascular agerelatedmacular degeneration (AMD.Methods: 35 patients with wet AMD undergone intravitreal 0.5 mg ranibizumab injection. Color Doppler Imaging (CDI and dopplerographywere used to measure hemodynamic parameters including the peak systolic velocity (Vsyst, cm / s, end-diastolic velocity (V diast, cm / s, and resistance index (RI of blood flow in the central retinal artery (CRA, the short posterior ciliary arteries (PCA, and the ophthalmic artery (OA. All patients were examined before and after injection on day 1‑7 and 30 day during the 3‑month follow up period.Results: Before intravitreal injection Vsyst was decreased in short PCA (p<0.05, RI in CRA and in short PCA significantly increased in comparison with normal index in same vessels. The peak systolic velocity in OA, in CRA and in short PCA was not significantly changed. After second inje