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Rosen E.,Meir Medical Center | Sachs D.,Goldschleger Eye Research Institute | Eliahu S.B.,Harlan Biotech Israel | Assia E.I.,Meir Medical Center | Kleinmann G.,Kaplan Medical Center
Clinical and Experimental Ophthalmology | Year: 2013

To assess the surgical procedure, safety and stability of a next generation injectable telescope prosthesis in a rabbit model. Methods: After removal of the crystalline lenses of eight New Zealand White rabbits, the next generation device was randomly implanted in one eye, and the available telescope prosthesis (Normal device) was implanted in the fellow eye. Operative parameters (incision, capsulorrhexis size and operative time), intraoperative and postoperative complications rates, endothelial cell density changes and the distance between the corneal endothelium and the telescope (central clearance distance) were measured and compared between the groups. Results: Incision size and capsulorrhexis size were smaller, and operative time was shorter in the next generation group in comparison with the Normal group. No difference was found in the intraoperative and postoperative complication rates between the groups. Endothelial cell density loss observed in the next generation group was less than the loss in the Normal group, but the difference was not significant statistically. The central clearance distance was significantly larger in the next generation group in comparison with the Normal group (P=0.001). Conclusions: The next generation telescope was implanted through a smaller incision, with a shorter surgical time and a larger central clearance distance in the rabbit eyes, in comparison with the Normal group. The next generation device may allow reduced trauma to the corneal endothelium, better control during surgery and induce less astigmatism while preserving the optical advantages of the Food and Drug Administration-approved telescope prosthesis. © 2012 The Authors Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.


Pras E.,Assaf Harofeh Medical Center | Pras E.,Tel Aviv University | Pras E.,Gartner | Reznik-Wolf H.,Gartner | And 8 more authors.
Molecular Vision | Year: 2012

Purpose: To characterize the genetic defects associated with fundus albipunctatus (FAP) in patients in Israel. Methods: Twenty patients with FAP from diverse ethnicities underwent ophthalmic and electroretinogram tests following the International Society for Clinical Electrophysiology of Vision protocol. Genomic DNA was extracted from peripheral blood. Mutation analysis of the 11-cis retinol dehydrogenase (RDH5) gene was performed with direct sequencing of PCRamplified exons. Results: Four novel RDH5 gene mutations were identified. Of them, the null mutations c.343C>T (p.R54X) and c. 242delTGCC were most prevalent. Macular involvement was present in two patients who carry different mutation types. Conclusions: Mutation analysis of the RDH5 gene in the present series revealed four novel mutations and a previously reported one. No significant genotype-phenotype correlation was found. © 2012 Molecular Vision.


Golberg A.,Hebrew University of Jerusalem | Kandel J.,Yeshiva University | Belkin M.,Goldschleger Eye Research Institute | Rubinsky B.,University of California at Berkeley
IEEE Transactions on Plasma Science | Year: 2010

This paper introduces a new concept and method for long-term sterile storage of turbid product, which is potentially subject to microbial contamination. The method uses intermittent delivery of pulsed electric fields (IDPEF) throughout the storage at time intervals that are prescribed according to microorganisms' growth kinetics. This new approach facilitates sterile storage without the need for chemical preservatives, additives, radiation or the complex infrastructure demanded by refrigeration. Unlike ultraviolet radiation, IDPEF can be used in turbid media. The first part of this paper is a theoretical discussion on the growth kinetics of microorganisms treated by IDPEF. We then provide a preliminary experimental study on the kinetics of microorganism growth in a turbid microbial growth media as a function of the IDPEF delivery intervals. Last, we demonstrate the use of the method using milk as a medium. IDPEF of 30 pulses, 17.5 kV/cm field strength, 40 μ long, 1 Hz delivered every 12 h was found to have the ability to preserve milk in a non-sterile environment at room temperature as effectively as refrigeration at 4 °C. The method has many obvious applications in biotechnology, the food industry, and is of particular importance with regard to geographical areas lacking refrigeration for storage of pharmaceuticals and food. This study was performed on the laboratory scale and a substantial adaptations are required in order to apply it to the industrial scale. © 2006 IEEE.


Levi M.,Tel Aviv University | Tzabari M.,Tel Aviv University | Savion N.,Goldschleger Eye Research Institute | Savion N.,Tel Aviv University | And 5 more authors.
Reproduction | Year: 2015

Infertility induced by anti-cancer treatments pose a major concern for cancer survivors. Doxorubicin (DXR) has been previously shown to exert toxic effects on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we studied its potential effect in reducing DXR-induced testicular toxicity. Male mice were injected with 5 mg/kg DXR, 100 mg/kg DEX, combination of both or saline (control) and sacrificed either 1, 3 or 6 months later. Testes were excised and further processed. Glutathione and apoptosis assays were performed to determine oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effects of the drugs on testicular histology and on spermatogonial reserve. DXR and the combined treatment induced a striking decline in testicular weight. DEX prevented DXR-induced oxidative stress, but enhanced DXR-induced apoptosis within the testes. Furthermore, the combined treatment depleted the spermatogonial reserve after 1 month, with impaired recovery at 3 and 6 months post-treatment. This resulted in compromised sperm parameters, testicular and epididymal weights as well as significantly reduced sperm motility, all of which were more severe than those observed in DXR-treated mice. The activity of DEX in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR exacerbates DXR-induced testicular toxicity. © 2015 Society for Reproduction and Fertility.


Skaat A.,Tel Aviv University | Solomon A.,Tel Aviv University | Moroz I.,Tel Aviv University | Hai O.V.,Tel Aviv University | And 4 more authors.
Acta Ophthalmologica | Year: 2011

Purpose: To assess the effect of bevacizumab (Avastin®), a vascular endothelial growth factor inhibitor, on retinal function by full-field electroretinography (ERG) in patients with neovascular age-related macular degeneration (AMD). Design: A prospective, nonrandomized, controlled interventional clinical trial. Methods: Twelve patients (aged 50-85) with neovascular AMD each received one unilateral intravitreal injection of bevacizumab 1.25 mg/0.05 ml as part of the standard management for choroidal neovascular AMD. Before and 1 month after injection, all patients underwent bilateral full-field ERG scanning by a masked technician according to the ISCEV protocol, and their wave amplitudes were recorded. Untreated eyes served as controls. Scotopic responses were recorded at four incremental light intensities and photopic responses at two incremental light intensities. Changes in ERG-amplitude responses were calculated. Repeated-measures anova was used for data analysis. Results: Mean pre- and postinjection differences in a-wave amplitudes between the incremental light intensities in injected eyes were significantly higher than in controls (15.92 versus 1.33 μV for scotopic responses and 4.97 versus -1.06 μV for photopic responses; p = 0.057 and p = 0.01, respectively). Mean b-wave amplitudes in injected eyes were significantly higher than in controls for photopic responses (p = 0.048), but for scotopic responses, the difference between treated and untreated eyes was not significant (p = 0.23). Conclusions: Intravitreally injected bevacizumab improves both rod and cone functioning in patients with neovascular AMD, as demonstrated by the increase in the ERG a-wave responses of these patients. Other measured ERG parameters yielded no significant photoreceptor toxicity. © 2010 The Authors. Acta Ophthalmologica.


Izigov N.,Goldschleger Eye Research Institute | Izigov N.,Tel Aviv University | Farzam N.,Goldschleger Eye Research Institute | Farzam N.,Tel Aviv University | And 2 more authors.
Free Radical Biology and Medicine | Year: 2011

Oxidative stress and/or low cellular glutathione (GSH) levels are associated with the development and progression of numerous pathological conditions. Cells possess various antioxidant protection mechanisms, including GSH and phase II detoxifying enzymes. N-acetylcysteine (NAC) supplies cells with cysteine to increase GSH level but its efficacy is relatively low because of its limited tissue penetration. Allicin (diallyl thiosulfinate), a reactive sulfaorganic compound, increases cellular GSH and phase II detoxifying enzymes in vascular endothelial cells (EC). A novel compound was designed: S-allylmercapto-N-acetylcysteine (ASSNAC), a conjugate of S-allyl mercaptan (a component of allicin) and NAC. Both ASSNAC and NAC increased cellular GSH of ECs, reaching a maximum of up to four- and threefold increase after exposure for 24 or 6 h at a concentration of 0.2 or 1 mM, respectively. ASSNAC induced nuclear translocation of the activated transcription factor Nrf2 and expression of phase II detoxifying enzymes. EC exposure to tBuOOH resulted in 75% cytotoxicity, and pretreatment of cultures with 0.2 mM ASSNAC or 2 mM NAC reduced cytotoxicity to 20 and 42%, respectively. In conclusion, ASSNAC is superior to NAC in protecting cells from oxidative stress because of its ability to up-regulate both GSH and the expression of phase II detoxifying enzymes. © 2010 Elsevier Inc. All rights reserved.


Rotenstreich Y.,Goldschleger Eye Research Institute | Skaat A.,Goldschleger Eye Research Institute | Sher I.,Goldschleger Eye Research Institute | Kolker A.,Goldschleger Eye Research Institute | And 3 more authors.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2014

Evaluation of visual field (VF) is important for clinical diagnosis and patient monitoring. The current VF methods are subjective and require patient cooperation. Here we developed a novel objective perimetry technique based on the pupil response (PR) to multifocal chromatic stimuli in normal subjects and in patients with glaucoma and retinitis pigmentosa (RP). A computerized infrared video pupillometer was used to record PR to short- and long-wavelength stimuli (peak 485 nm and 620 nm, respectively) at light intensities of 15-100 cd-s/m2 at thirteen different points of the VF. The RP study included 30 eyes of 16 patients and 20 eyes of 12 healthy participants. The glaucoma study included 22 eyes of 11 patients and 38 eyes of 19 healthy participants. Significantly reduced PR was observed in RP patients in response to short-wavelength stimuli at 40 cd-s/m2 in nearly all perimetric locations (P <0.05). By contrast, RP patients demonstrated nearly normal PR to long-wavelength in majority of perimetric locations. The glaucoma group showed significantly reduced PR to long- and short-wavelength stimuli at high intensity in all perimetric locations (P <0.05). The PR of glaucoma patients was significantly lower than normal in response to short-wavelength stimuli at low intensity mostly in central and 20° locations (p<0.05). This study demonstrates the feasibility of using pupillometer-based chromatic perimetry for objectively assessing VF defects and retinal function and optic nerve damage in patients with retinal dystrophies and glaucoma. Furthermore, this method may be used to distinguish between the damaged cells underlying the VF defect.


PubMed | Goldschleger Eye Research Institute
Type: Controlled Clinical Trial | Journal: Acta ophthalmologica | Year: 2011

To assess the effect of bevacizumab (Avastin), a vascular endothelial growth factor inhibitor, on retinal function by full-field electroretinography (ERG) in patients with neovascular age-related macular degeneration (AMD).A prospective, nonrandomized, controlled interventional clinical trial.Twelve patients (aged 50)85) with neovascular AMD each received one unilateral intravitreal injection of bevacizumab 1.25 mg 0.05 ml as part of the standard management for choroidal neovascular AMD. Before and 1 month after injection, all patients underwent bilateral full-field ERG scanning by a masked technician according to the ISCEV protocol, and their wave amplitudes were recorded. Untreated eyes served as controls. Scotopic responses were recorded at four incremental light intensities and photopic responses at two incremental light intensities. Changes in ERG-amplitude responses were calculated. Repeated-measures ANOVA was used for data analysis.Mean pre- and postinjection differences in a-wave amplitudes between the incremental light intensities in injected eyes were significantly higher than in controls (15.92 versus 1.33 lV for scotopic responses and 4.97 versus )1.06 lV for photopic responses; p = 0.057 and p = 0.01, respectively). Mean b-wave amplitudes in injected eyes were significantly higher than in controls for photopic responses (p = 0.048), but for scotopic responses, the difference between treated and untreated eyes was not significant (p = 0.23).Intravitreally injected bevacizumab improves both rod and cone functioning in patients with neovascular AMD, as demonstrated by the increase in the ERG a-wave responses of these patients. Other measured ERG parameters yielded no significant photoreceptor toxicity.


PubMed | Goldschleger Eye Research Institute
Type: Journal Article | Journal: Free radical biology & medicine | Year: 2011

Oxidative stress and/or low cellular glutathione (GSH) levels are associated with the development and progression of numerous pathological conditions. Cells possess various antioxidant protection mechanisms, including GSH and phase II detoxifying enzymes. N-acetylcysteine (NAC) supplies cells with cysteine to increase GSH level but its efficacy is relatively low because of its limited tissue penetration. Allicin (diallyl thiosulfinate), a reactive sulfaorganic compound, increases cellular GSH and phase II detoxifying enzymes in vascular endothelial cells (EC). A novel compound was designed: S-allylmercapto-N-acetylcysteine (ASSNAC), a conjugate of S-allyl mercaptan (a component of allicin) and NAC. Both ASSNAC and NAC increased cellular GSH of ECs, reaching a maximum of up to four- and threefold increase after exposure for 24 or 6 h at a concentration of 0.2 or 1 mM, respectively. ASSNAC induced nuclear translocation of the activated transcription factor Nrf2 and expression of phase II detoxifying enzymes. EC exposure to tBuOOH resulted in 75% cytotoxicity, and pretreatment of cultures with 0.2 mM ASSNAC or 2mM NAC reduced cytotoxicity to 20 and 42%, respectively. In conclusion, ASSNAC is superior to NAC in protecting cells from oxidative stress because of its ability to up-regulate both GSH and the expression of phase II detoxifying enzymes.

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