The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Ido Perlman - One of the best experts on this subject based on the ideXlab platform.
-
Infliximab exerts a dose-dependent effect on retinal safety in the Albino Rabbit
Documenta Ophthalmologica, 2017Co-Authors: Shiri Zayit-soudry, Esther Zemel, Ido Perlman, Igor Vainer, Michael Mimouni, Melvin Rabena, Dante J. Pieramici, Anat LoewensteinAbstract:Purpose To assess the retinal toxicity of an intravitreal injection of infliximab, a monoclonal antibody to tumor necrosis factor α, in a Rabbit model. Materials and methods Two groups of adult Albino Rabbits ( n = 5) received intravitreal injections of infliximab (0.1 ml) in the study eye and balanced salt solution (BSS, 0.1 ml) in the control eye at baseline. Group 1 was administered with 1.5 mg/0.1 ml, and group 2 was injected with 7.5 mg/0.1 ml of infliximab solution. Electroretinography (ERG) was performed at baseline and at 1, 7, 30, and 45 days after the injection. Visual evoked potentials (VEPs) were recorded at 7 and 45 days after the injection. After the last electrophysiological assessment, the Rabbits were euthanized and retinal histopathology and immunhistochemistry for glial fibrillary acidic protein (GFAP) were performed. Results ERG responses demonstrated no significant deficit in retinal function in eyes injected with infliximab. Mean dark-adapted a-wave and b-wave maximal amplitude and semi-saturation constant values at baseline and throughout the 45 days of follow-up after the injection indicated no remarkable difference in outer retinal function between the control and experimental eyes. VEP responses were similar at each time point (7 and 45 days). No difference was seen in retinal histopathology and immunocytochemistry sections in eyes receiving the 1.5 mg/0.1 ml dose compared to the control eyes. However, increased GFAP labeling in retinal Müller cells was detected in Rabbit eyes treated with the 7.5 mg/0.1 ml dose. Conclusions Intravitreal injection of 1.5 mg/0.1 ml infliximab dose has no toxic effect on the integrity (functional or structural) of the retina in Rabbits. A higher dose of 7.5 mg/0.1 ml may be slightly toxic as suggested by positive Müller cell GFAP expression. Additional studies of retinal toxicity at higher doses and after multiple injections are needed to establish the retinal safety of intravitreal infliximab therapy in humans.
-
infliximab exerts a dose dependent effect on retinal safety in the Albino Rabbit
Documenta Ophthalmologica, 2017Co-Authors: Shiri Zayitsoudry, Esther Zemel, Ido Perlman, Igor Vainer, Michael Mimouni, Melvin Rabena, Dante J. PieramiciAbstract:To assess the retinal toxicity of an intravitreal injection of infliximab, a monoclonal antibody to tumor necrosis factor α, in a Rabbit model. Two groups of adult Albino Rabbits (n = 5) received intravitreal injections of infliximab (0.1 ml) in the study eye and balanced salt solution (BSS, 0.1 ml) in the control eye at baseline. Group 1 was administered with 1.5 mg/0.1 ml, and group 2 was injected with 7.5 mg/0.1 ml of infliximab solution. Electroretinography (ERG) was performed at baseline and at 1, 7, 30, and 45 days after the injection. Visual evoked potentials (VEPs) were recorded at 7 and 45 days after the injection. After the last electrophysiological assessment, the Rabbits were euthanized and retinal histopathology and immunhistochemistry for glial fibrillary acidic protein (GFAP) were performed. ERG responses demonstrated no significant deficit in retinal function in eyes injected with infliximab. Mean dark-adapted a-wave and b-wave maximal amplitude and semi-saturation constant values at baseline and throughout the 45 days of follow-up after the injection indicated no remarkable difference in outer retinal function between the control and experimental eyes. VEP responses were similar at each time point (7 and 45 days). No difference was seen in retinal histopathology and immunocytochemistry sections in eyes receiving the 1.5 mg/0.1 ml dose compared to the control eyes. However, increased GFAP labeling in retinal Muller cells was detected in Rabbit eyes treated with the 7.5 mg/0.1 ml dose. Intravitreal injection of 1.5 mg/0.1 ml infliximab dose has no toxic effect on the integrity (functional or structural) of the retina in Rabbits. A higher dose of 7.5 mg/0.1 ml may be slightly toxic as suggested by positive Muller cell GFAP expression. Additional studies of retinal toxicity at higher doses and after multiple injections are needed to establish the retinal safety of intravitreal infliximab therapy in humans.
-
Safety of intravitreal clindamycin in Albino Rabbit eyes.
Documenta ophthalmologica. Advances in ophthalmology, 2017Co-Authors: Zohar Habot-wilner, Anat Loewenstein, Orit Mazza, Jonathan Shahar, Amir Massarweh, Irit Mann, Ido PerlmanAbstract:To study the potential toxic effects of intravitreal clindamycin on the retina of Albino Rabbits, by assessing functional and morphological retinal changes. Eight Albino Rabbits were included in the study. In each Rabbit, 1 mg/0.1 ml clindamycin was injected into the vitreous of the right (experimental) eye, and 0.1 ml saline was injected into the vitreous of the left (control) eye. The electroretinogram (ERG) was recorded before injection, 3 days, 1, 2, and 4 weeks post-injection. The visual evoked potential (VEP) was recorded 4 weeks post-injection. Clinical examination was conducted at all time points. The eyes were enucleated at the termination of the follow-up period in order to prepare the retinas for histology in order to assess retinal structure. ERG and VEP responses that were recorded from the experimental eye at different times following intravitreal clindamycin injection were very similar to the corresponding responses that were recorded from the control eyes. Clinical examination was normal in all eyes, and no histological damage was observed. Intravitreal injection of 1 mg clindamycin does not cause functional or morphological signs of retinal toxicity in Albino Rabbits, during a period of 4 weeks post-injection. These findings support the clinical use of 1 mg intravitreal clindamycin.
-
physiological and toxicological effects of cefuroxime on the Albino Rabbit retina
Investigative Ophthalmology & Visual Science, 2012Co-Authors: Jonathan Shahar, Ido Perlman, Esther Zemel, Anat LoewensteinAbstract:PURPOSE Intracameral cefuroxime was found to lower the risk of endophthalmitis after cataract surgery. The purpose of this study was to evaluate the retinal toxicity of cefuroxime in a Rabbit model. METHODS Twenty-two Albino Rabbits were divided into two cefuroxime groups: low-dose (1mg/0.1 mL, n = 9) and high dose (10 mg/0.1 mL, n = 13). The right eye of each Rabbit was injected with 0.1 mL cefuroxime solution (experimental eye) and the left eye with 0.1 mL saline (control eye). Electroretinogram (ERG) responses were recorded at 3 hours, 4 days, and 1, 2, and 4 weeks after injection. After 4 weeks, the Rabbits were euthanized, the eyes were enucleated, and the retinas were prepared for histologic evaluation and GFAP immunostaining. RESULTS No functional (ERG) or histologic damage was found in Rabbits in the low-dose group. In the high-dose group, a significant decrease in the ERG amplitudes of the experimental eyes was seen 3 hours after injection, followed by partial recovery during 4 weeks of follow-up. Retinal histology of experimental eyes revealed marked damage. GFAP immunoreactivity in Muller cells was expressed in Rabbits belonging to both groups, although it was more extensive in the high-dose group. CONCLUSIONS ERG and histologic findings indicated that a dose of 1 mg cefuroxime, administered intravitreally, was not toxic to the Rabbit retina. A dose of 10 mg, injected intravitreally, induced transient physiological effects, and was toxic to the Rabbit retina, as was evident by the permanent reduction in the ERG responses and by the structural damage to the retina with signs of glial activation.
-
Drug-induced retinal toxicity in Albino Rabbits: the effects of imipenem and aztreonam.
Investigative ophthalmology & visual science, 1993Co-Authors: Anat Loewenstein, Esther Zemel, Moshe Lazar, Ido PerlmanAbstract:PURPOSE: To test the toxic action of two antibiotics, imipenem and aztreonam, on the functional and morphologic integrity of the Albino Rabbit retina. METHODS: Two commercial drugs were used--Tienam, which contains imipenem, and Azactam, which contains aztreonam. Different doses of these drugs were injected intravitreally. Retinal function was assessed from the electroretinogram (ERG) and the visual evoked potential (VEP). Retinal structure was examined at the light microscopic level. RESULTS: Imipenem did not affect the ERG and the VEP responses or the morphology of the retina up to a total injected dose of 0.98 mg (2 mg Tienam). Aztreonam was not toxic to the Albino Rabbit retina up to a total injected dose of 2.8 mg (5 mg of Azactam). Severe functional and morphologic retinal damage was seen when 10 mg of Azactam was injected. A similar degree of damage was seen when a dose of 5 mg L-arginine, an ingredient of Azactam, was injected into the vitreous. CONCLUSIONS: Imipenem and aztreonam are nontoxic to the Albino Rabbit retina at concentrations that are 500-fold higher than their effective dose against bacterial infection. Azactam is highly toxic at high levels (more than 10 mg injected into the vitreous). Most of the toxicity could be explained by the L-arginine content of the drug.
Anat Loewenstein - One of the best experts on this subject based on the ideXlab platform.
-
Infliximab exerts a dose-dependent effect on retinal safety in the Albino Rabbit
Documenta Ophthalmologica, 2017Co-Authors: Shiri Zayit-soudry, Esther Zemel, Ido Perlman, Igor Vainer, Michael Mimouni, Melvin Rabena, Dante J. Pieramici, Anat LoewensteinAbstract:Purpose To assess the retinal toxicity of an intravitreal injection of infliximab, a monoclonal antibody to tumor necrosis factor α, in a Rabbit model. Materials and methods Two groups of adult Albino Rabbits ( n = 5) received intravitreal injections of infliximab (0.1 ml) in the study eye and balanced salt solution (BSS, 0.1 ml) in the control eye at baseline. Group 1 was administered with 1.5 mg/0.1 ml, and group 2 was injected with 7.5 mg/0.1 ml of infliximab solution. Electroretinography (ERG) was performed at baseline and at 1, 7, 30, and 45 days after the injection. Visual evoked potentials (VEPs) were recorded at 7 and 45 days after the injection. After the last electrophysiological assessment, the Rabbits were euthanized and retinal histopathology and immunhistochemistry for glial fibrillary acidic protein (GFAP) were performed. Results ERG responses demonstrated no significant deficit in retinal function in eyes injected with infliximab. Mean dark-adapted a-wave and b-wave maximal amplitude and semi-saturation constant values at baseline and throughout the 45 days of follow-up after the injection indicated no remarkable difference in outer retinal function between the control and experimental eyes. VEP responses were similar at each time point (7 and 45 days). No difference was seen in retinal histopathology and immunocytochemistry sections in eyes receiving the 1.5 mg/0.1 ml dose compared to the control eyes. However, increased GFAP labeling in retinal Müller cells was detected in Rabbit eyes treated with the 7.5 mg/0.1 ml dose. Conclusions Intravitreal injection of 1.5 mg/0.1 ml infliximab dose has no toxic effect on the integrity (functional or structural) of the retina in Rabbits. A higher dose of 7.5 mg/0.1 ml may be slightly toxic as suggested by positive Müller cell GFAP expression. Additional studies of retinal toxicity at higher doses and after multiple injections are needed to establish the retinal safety of intravitreal infliximab therapy in humans.
-
Safety of intravitreal clindamycin in Albino Rabbit eyes.
Documenta ophthalmologica. Advances in ophthalmology, 2017Co-Authors: Zohar Habot-wilner, Anat Loewenstein, Orit Mazza, Jonathan Shahar, Amir Massarweh, Irit Mann, Ido PerlmanAbstract:To study the potential toxic effects of intravitreal clindamycin on the retina of Albino Rabbits, by assessing functional and morphological retinal changes. Eight Albino Rabbits were included in the study. In each Rabbit, 1 mg/0.1 ml clindamycin was injected into the vitreous of the right (experimental) eye, and 0.1 ml saline was injected into the vitreous of the left (control) eye. The electroretinogram (ERG) was recorded before injection, 3 days, 1, 2, and 4 weeks post-injection. The visual evoked potential (VEP) was recorded 4 weeks post-injection. Clinical examination was conducted at all time points. The eyes were enucleated at the termination of the follow-up period in order to prepare the retinas for histology in order to assess retinal structure. ERG and VEP responses that were recorded from the experimental eye at different times following intravitreal clindamycin injection were very similar to the corresponding responses that were recorded from the control eyes. Clinical examination was normal in all eyes, and no histological damage was observed. Intravitreal injection of 1 mg clindamycin does not cause functional or morphological signs of retinal toxicity in Albino Rabbits, during a period of 4 weeks post-injection. These findings support the clinical use of 1 mg intravitreal clindamycin.
-
physiological and toxicological effects of cefuroxime on the Albino Rabbit retina
Investigative Ophthalmology & Visual Science, 2012Co-Authors: Jonathan Shahar, Ido Perlman, Esther Zemel, Anat LoewensteinAbstract:PURPOSE Intracameral cefuroxime was found to lower the risk of endophthalmitis after cataract surgery. The purpose of this study was to evaluate the retinal toxicity of cefuroxime in a Rabbit model. METHODS Twenty-two Albino Rabbits were divided into two cefuroxime groups: low-dose (1mg/0.1 mL, n = 9) and high dose (10 mg/0.1 mL, n = 13). The right eye of each Rabbit was injected with 0.1 mL cefuroxime solution (experimental eye) and the left eye with 0.1 mL saline (control eye). Electroretinogram (ERG) responses were recorded at 3 hours, 4 days, and 1, 2, and 4 weeks after injection. After 4 weeks, the Rabbits were euthanized, the eyes were enucleated, and the retinas were prepared for histologic evaluation and GFAP immunostaining. RESULTS No functional (ERG) or histologic damage was found in Rabbits in the low-dose group. In the high-dose group, a significant decrease in the ERG amplitudes of the experimental eyes was seen 3 hours after injection, followed by partial recovery during 4 weeks of follow-up. Retinal histology of experimental eyes revealed marked damage. GFAP immunoreactivity in Muller cells was expressed in Rabbits belonging to both groups, although it was more extensive in the high-dose group. CONCLUSIONS ERG and histologic findings indicated that a dose of 1 mg cefuroxime, administered intravitreally, was not toxic to the Rabbit retina. A dose of 10 mg, injected intravitreally, induced transient physiological effects, and was toxic to the Rabbit retina, as was evident by the permanent reduction in the ERG responses and by the structural damage to the retina with signs of glial activation.
-
Drug-induced retinal toxicity in Albino Rabbits: the effects of imipenem and aztreonam.
Investigative ophthalmology & visual science, 1993Co-Authors: Anat Loewenstein, Esther Zemel, Moshe Lazar, Ido PerlmanAbstract:PURPOSE: To test the toxic action of two antibiotics, imipenem and aztreonam, on the functional and morphologic integrity of the Albino Rabbit retina. METHODS: Two commercial drugs were used--Tienam, which contains imipenem, and Azactam, which contains aztreonam. Different doses of these drugs were injected intravitreally. Retinal function was assessed from the electroretinogram (ERG) and the visual evoked potential (VEP). Retinal structure was examined at the light microscopic level. RESULTS: Imipenem did not affect the ERG and the VEP responses or the morphology of the retina up to a total injected dose of 0.98 mg (2 mg Tienam). Aztreonam was not toxic to the Albino Rabbit retina up to a total injected dose of 2.8 mg (5 mg of Azactam). Severe functional and morphologic retinal damage was seen when 10 mg of Azactam was injected. A similar degree of damage was seen when a dose of 5 mg L-arginine, an ingredient of Azactam, was injected into the vitreous. CONCLUSIONS: Imipenem and aztreonam are nontoxic to the Albino Rabbit retina at concentrations that are 500-fold higher than their effective dose against bacterial infection. Azactam is highly toxic at high levels (more than 10 mg injected into the vitreous). Most of the toxicity could be explained by the L-arginine content of the drug.
Vincent H.l. Lee - One of the best experts on this subject based on the ideXlab platform.
-
Ocular esterase composition in Albino and pigmented Rabbits: Possible implications in ocular prodrug design and evaluation
Current Eye Research, 2009Co-Authors: Vincent H.l. Lee, Shih-chieh Chang, Clarence M. Oshiro, Ronald E. SmithAbstract:A methodology was developed to determine the proportion of acetyl-(AChE) and butyrylcholinesterase (BuChE) in the Albino and pigmented Rabbit eye. It was found that BuChE contributed over 75% of the cholinesterase activity in all the ocular tissues but the corneal epithelium of the Albino Rabbit. This esterase was principally responsible for the parabolic chain length dependence of ocular hydrolysis of model naphthyl ester prodrugs reported previously. In contrast, when incubated with AChE, the rate of hydrolysis of these esters decreased monotonically with increasing ester chain length. Together these findings suggest that esters whose chain length exceeds 4 carbons will be hydrolyzed primarily by BuChE. It is suggested that the dominance of BuChE in ocular tissues is another factor which merits consideration in the design and evaluation of ocular ester prodrugs.
-
paracellular transport of a proteolytically labile pentapeptide across the colonic and other intestinal segments of the Albino Rabbit implications for peptide drug design
Journal of Controlled Release, 1994Co-Authors: Yen Wanching, Vincent H.l. LeeAbstract:The objective of this study was to determine whether a pentapeptide susceptible to intracellular collagenase action, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (Pz-peptide), would be able to penetrate the colonic and other intestinal segments of the Albino Rabbit essentially intact. Incubation of Pz-peptide with homogenates and subcellular fractions of various intestinal segments revealed that this peptide was most susceptible to degradation in the descending colon and least so in the jejunum. About 60% of the proteolytic activity against Pz-peptide was cytosolic. Nevertheless, Pzpeptide penetrated all intestinal segments with more than 80% of it in the intact form. Although Pzpeptide was most susceptible to proteolysis in the descending colon, its penetration was the second best there. Furthermore, the extent of penetration of both Pz-peptide and its hydrolytic product, Pz-Pro-Leu, was as well as or even better than that of more lipophilic atenolol, timolol and propranolol. Escape of Pz-peptide from the surveillance by intracellular collagenases, especially in the descending colon, suggests that Pz-peptide was mainly transported by the paracellular pathway, perhaps by enhancing tight junctional permeability. Such a possibility was supported by (a) no correlation between extent of Pz-peptide penetration and collagenase activity in various intestinal segments, (b) concentration-dependent Pz-peptide transport in the colon and rectum and (c) Pz-peptide-induced increase in the penetration of hydrophilic mannitol and atenolol and decrease in transepithelial electrical resistance in Caco-2 monolayers. The above findings suggest that it may be possible to design peptides that would instinctively seek out the paracellular pathway of transport, thereby escaping intracellular proteolytic processing.
-
segmental differences in drug permeability esterase activity and ketone reductase activity in the Albino Rabbit intestine
Journal of Drug Targeting, 1993Co-Authors: Milind Narawane, Samir K Podder, Hans Bundgaard, Vincent H.l. LeeAbstract:AbstractPossible segmental differences in drug permeability as well as esterase and ketone reductase activities in the Albino Rabbit intestine were investigated. Beta adrenergic antagonists and timolol prodrugs spanning four orders of magnitude in distribution coefficient were used as model drugs. Drug penetration was evaluated in Ussing chambers using isolated segments of the duodenum, jejunum, ileum, ascending colon, descending colon, and rectum. Esterase and ketone reductase activities were determined in homogenates of the above segments using timolol ester prodrugs and levobunolol as substrates, respectively. The results indicate that the hydrophilic beta adrenergic antagonists atenolol and sotalol and moderately lipophilic metoprolol penetrated all intestinal segments equally well, whereas moderately lipophilic timolol and lipophilic propranolol, levobunolol and betaxolol were better absorbed from the large than from the small intestinal segments. Changes in lipophilicity exerted a more pronounced ef...
-
a mechanistic study on enhancement of rectal permeability to insulin in the Albino Rabbit
Journal of Pharmacology and Experimental Therapeutics, 1992Co-Authors: A. Yamamoto, E Hayakawa, Y Kato, A Nishiura, Vincent H.l. LeeAbstract:This study was conducted mainly to investigate the relative contributions of various mechanisms by which bile salts and EDTA may improve the in vitro rectal penetration of insulin in the Albino Rabbit. Insulin could not cross the rectal mucosa unless Na glycocholate or other penetration enhancers were present. Penetration enhancement was attributed primarily to Na glycocholate's ability to reduce the barrier function of the rectal membrane and to increase the fraction of insulin in its monomeric form, and secondarily to Na glycocholate's ability to protect insulin from proteolysis. Na glycocholate was more effective than Na taurocholate, but less effective than Na deoxycholate and polyoxyethylene-9-lauryl ether in enhancing rectal insulin penetration. Although EDTA at 0.01 and 0.1% did not affect rectal insulin penetration, it augmented the penetration enhancement effect of 1% Na glycocholate without causing additional damage to the rectal membrane, as judged by protein release. Such an action was attributed to the synergistic effect associated with: 1) an increase in the permeability of the paracellular pathway by EDTA and 2) an increase in the proportion of insulin in the monomeric form by Na glycocholate. Results from parallel in vivo experiments have indicated that it may be possible to achieve significant penetration enhancement by using a combination of otherwise membrane-damaging penetration enhancers which act by complementary mechanisms at concentrations that are both effective and well tolerated by mucosal epithelial cells.
-
conjunctival penetration of insulin and peptide drugs in the Albino Rabbit
Pharmaceutical Research, 1992Co-Authors: Eiji Hayakawa, Wei Wang, Akira Yamamoto, Dushieng Chien, Kazuhiro Inagaki, Vincent H.l. LeeAbstract:An in vitro model was used to evaluate the conjunctival penetration of three peptides, [D-ala2]metenkephalinamide (YAGFM, MW 647), substance P (MW 1348), and insulin (MW 5778), in comparison with two nonpeptides, atenolol (MW 266) and timolol (MW 433). All three peptides were hydrolyzed to varying extents during penetration across the conjunctiva. The permeability coefficient for intact YAGFM and insulin was 4.5 ± 0.3 and 4.6 ± 0.7 µm sec−1, respectively. These values were about two to five times lower than those for atenolol and timolol. No permeability coefficient could be calculated for substance P, since its transconjunctival flux never reached steady state. The conjunctival penetration of YAGFM and insulin was improved by about two and three times, respectively, with the addition of 1% Na glycocholate. Increasing the Na glycocholate concentration was more effective than changing the type of bile salt in improving the conjunctival penetration of insulin. The maximum factor of improvement was 12, as the Na glycocholate concentration was raised to 4%. The way in which Na deoxycholate, glycocholate, and taurocholate affected the conjunctival penetration of atenolol, timolol, and insulin suggests that these three bile salts improved mainly the transcellular penetration of the compounds studied.
Esther Zemel - One of the best experts on this subject based on the ideXlab platform.
-
Infliximab exerts a dose-dependent effect on retinal safety in the Albino Rabbit
Documenta Ophthalmologica, 2017Co-Authors: Shiri Zayit-soudry, Esther Zemel, Ido Perlman, Igor Vainer, Michael Mimouni, Melvin Rabena, Dante J. Pieramici, Anat LoewensteinAbstract:Purpose To assess the retinal toxicity of an intravitreal injection of infliximab, a monoclonal antibody to tumor necrosis factor α, in a Rabbit model. Materials and methods Two groups of adult Albino Rabbits ( n = 5) received intravitreal injections of infliximab (0.1 ml) in the study eye and balanced salt solution (BSS, 0.1 ml) in the control eye at baseline. Group 1 was administered with 1.5 mg/0.1 ml, and group 2 was injected with 7.5 mg/0.1 ml of infliximab solution. Electroretinography (ERG) was performed at baseline and at 1, 7, 30, and 45 days after the injection. Visual evoked potentials (VEPs) were recorded at 7 and 45 days after the injection. After the last electrophysiological assessment, the Rabbits were euthanized and retinal histopathology and immunhistochemistry for glial fibrillary acidic protein (GFAP) were performed. Results ERG responses demonstrated no significant deficit in retinal function in eyes injected with infliximab. Mean dark-adapted a-wave and b-wave maximal amplitude and semi-saturation constant values at baseline and throughout the 45 days of follow-up after the injection indicated no remarkable difference in outer retinal function between the control and experimental eyes. VEP responses were similar at each time point (7 and 45 days). No difference was seen in retinal histopathology and immunocytochemistry sections in eyes receiving the 1.5 mg/0.1 ml dose compared to the control eyes. However, increased GFAP labeling in retinal Müller cells was detected in Rabbit eyes treated with the 7.5 mg/0.1 ml dose. Conclusions Intravitreal injection of 1.5 mg/0.1 ml infliximab dose has no toxic effect on the integrity (functional or structural) of the retina in Rabbits. A higher dose of 7.5 mg/0.1 ml may be slightly toxic as suggested by positive Müller cell GFAP expression. Additional studies of retinal toxicity at higher doses and after multiple injections are needed to establish the retinal safety of intravitreal infliximab therapy in humans.
-
infliximab exerts a dose dependent effect on retinal safety in the Albino Rabbit
Documenta Ophthalmologica, 2017Co-Authors: Shiri Zayitsoudry, Esther Zemel, Ido Perlman, Igor Vainer, Michael Mimouni, Melvin Rabena, Dante J. PieramiciAbstract:To assess the retinal toxicity of an intravitreal injection of infliximab, a monoclonal antibody to tumor necrosis factor α, in a Rabbit model. Two groups of adult Albino Rabbits (n = 5) received intravitreal injections of infliximab (0.1 ml) in the study eye and balanced salt solution (BSS, 0.1 ml) in the control eye at baseline. Group 1 was administered with 1.5 mg/0.1 ml, and group 2 was injected with 7.5 mg/0.1 ml of infliximab solution. Electroretinography (ERG) was performed at baseline and at 1, 7, 30, and 45 days after the injection. Visual evoked potentials (VEPs) were recorded at 7 and 45 days after the injection. After the last electrophysiological assessment, the Rabbits were euthanized and retinal histopathology and immunhistochemistry for glial fibrillary acidic protein (GFAP) were performed. ERG responses demonstrated no significant deficit in retinal function in eyes injected with infliximab. Mean dark-adapted a-wave and b-wave maximal amplitude and semi-saturation constant values at baseline and throughout the 45 days of follow-up after the injection indicated no remarkable difference in outer retinal function between the control and experimental eyes. VEP responses were similar at each time point (7 and 45 days). No difference was seen in retinal histopathology and immunocytochemistry sections in eyes receiving the 1.5 mg/0.1 ml dose compared to the control eyes. However, increased GFAP labeling in retinal Muller cells was detected in Rabbit eyes treated with the 7.5 mg/0.1 ml dose. Intravitreal injection of 1.5 mg/0.1 ml infliximab dose has no toxic effect on the integrity (functional or structural) of the retina in Rabbits. A higher dose of 7.5 mg/0.1 ml may be slightly toxic as suggested by positive Muller cell GFAP expression. Additional studies of retinal toxicity at higher doses and after multiple injections are needed to establish the retinal safety of intravitreal infliximab therapy in humans.
-
physiological and toxicological effects of cefuroxime on the Albino Rabbit retina
Investigative Ophthalmology & Visual Science, 2012Co-Authors: Jonathan Shahar, Ido Perlman, Esther Zemel, Anat LoewensteinAbstract:PURPOSE Intracameral cefuroxime was found to lower the risk of endophthalmitis after cataract surgery. The purpose of this study was to evaluate the retinal toxicity of cefuroxime in a Rabbit model. METHODS Twenty-two Albino Rabbits were divided into two cefuroxime groups: low-dose (1mg/0.1 mL, n = 9) and high dose (10 mg/0.1 mL, n = 13). The right eye of each Rabbit was injected with 0.1 mL cefuroxime solution (experimental eye) and the left eye with 0.1 mL saline (control eye). Electroretinogram (ERG) responses were recorded at 3 hours, 4 days, and 1, 2, and 4 weeks after injection. After 4 weeks, the Rabbits were euthanized, the eyes were enucleated, and the retinas were prepared for histologic evaluation and GFAP immunostaining. RESULTS No functional (ERG) or histologic damage was found in Rabbits in the low-dose group. In the high-dose group, a significant decrease in the ERG amplitudes of the experimental eyes was seen 3 hours after injection, followed by partial recovery during 4 weeks of follow-up. Retinal histology of experimental eyes revealed marked damage. GFAP immunoreactivity in Muller cells was expressed in Rabbits belonging to both groups, although it was more extensive in the high-dose group. CONCLUSIONS ERG and histologic findings indicated that a dose of 1 mg cefuroxime, administered intravitreally, was not toxic to the Rabbit retina. A dose of 10 mg, injected intravitreally, induced transient physiological effects, and was toxic to the Rabbit retina, as was evident by the permanent reduction in the ERG responses and by the structural damage to the retina with signs of glial activation.
-
Drug-induced retinal toxicity in Albino Rabbits: the effects of imipenem and aztreonam.
Investigative ophthalmology & visual science, 1993Co-Authors: Anat Loewenstein, Esther Zemel, Moshe Lazar, Ido PerlmanAbstract:PURPOSE: To test the toxic action of two antibiotics, imipenem and aztreonam, on the functional and morphologic integrity of the Albino Rabbit retina. METHODS: Two commercial drugs were used--Tienam, which contains imipenem, and Azactam, which contains aztreonam. Different doses of these drugs were injected intravitreally. Retinal function was assessed from the electroretinogram (ERG) and the visual evoked potential (VEP). Retinal structure was examined at the light microscopic level. RESULTS: Imipenem did not affect the ERG and the VEP responses or the morphology of the retina up to a total injected dose of 0.98 mg (2 mg Tienam). Aztreonam was not toxic to the Albino Rabbit retina up to a total injected dose of 2.8 mg (5 mg of Azactam). Severe functional and morphologic retinal damage was seen when 10 mg of Azactam was injected. A similar degree of damage was seen when a dose of 5 mg L-arginine, an ingredient of Azactam, was injected into the vitreous. CONCLUSIONS: Imipenem and aztreonam are nontoxic to the Albino Rabbit retina at concentrations that are 500-fold higher than their effective dose against bacterial infection. Azactam is highly toxic at high levels (more than 10 mg injected into the vitreous). Most of the toxicity could be explained by the L-arginine content of the drug.
Ruponen Marika - One of the best experts on this subject based on the ideXlab platform.
-
Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in Rabbits
'Elsevier BV', 2020Co-Authors: Fayyaz Anam, Ranta Veli-pekka, Urtti Arto, Vellonen Kati-sisko, Ruponen Marika, Toropainen Elisa, Valtari Annika, Puranen Jooseppi, Gardner Iain, Jamei MasoudAbstract:Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics of a cocktail of three beta blockers after their topical administration into the Albino Rabbit eye. Samples from aqueous humour were analysed with LC-MS/MS. The pharmacokinetic parameters were estimated using compartmental and non-compartmental analyses. The ocular bioavailability was covering broad range of values: atenolol (0.07 %), timolol (1.22%, 1.51%) and betaxolol (3.82%, 4.31%). Absolute ocular bioavailability presented a positive trend with lipophilicity and the values showed approximately 60-fold range. The generated data enhances our understanding for ocular pharmacokinetics of drugs and may be utilized in pharmacokinetic model building in ophthalmic drug development.published versionpeerReviewe
-
Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in Rabbits
'Elsevier BV', 2020Co-Authors: Fayyaz Anam, Ranta Veli-pekka, Urtti Arto, Vellonen Kati-sisko, Ruponen Marika, Toropainen Elisa, Valtari Annika, Puranen Jooseppi, Gardner Iain, Jamei MasoudAbstract:Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics of a cocktail of three beta blockers after their topical administration into the Albino Rabbit eye. Samples from aqueous humour were analysed with LC-MS/MS. The pharmacokinetic parameters were estimated using compartmental and non-compartmental analyses. The ocular bioavailability was covering broad range of values: atenolol (0.07 %), timolol (1.22%, 1.51%) and betaxolol (3.82%, 4.31%). Absolute ocular bioavailability presented a positive trend with lipophilicity and the values showed approximately 60-fold range. The generated data enhances our understanding for ocular pharmacokinetics of drugs and may be utilized in pharmacokinetic model building in ophthalmic drug development.Peer reviewe
-
Esterase activity in porcine and Albino Rabbit ocular tissues
'Elsevier BV', 2018Co-Authors: Heikkinen, Emma M., Del Amo, Eva M., Ranta Veli-pekka, Urtti Arto, Vellonen Kati-sisko, Ruponen MarikaAbstract:Corneal esterases are utilized in the activation of topically applied ester prodrugs. Esterases may also be involved in the metabolism of drugs in posterior eye tissues, but their physiological activity is unknown. Furthermore, extrapolation of the esterase activity from protein level to the tissues is missing. The aims of the current study were to determine esterase activities in porcine and Albino Rabbit ocular tissues, calculate the activities for whole tissues and compare esterase activity between the species. We conducted a hydrolysis study with ocular tissue homogenates using an esterase probe substrate 4-nitrophenyl acetate. The hydrolysis rates were first normalized to protein content and then scaled to whole tissues. The hydrolytic rate normalized to protein content was high in the cornea and iris-ciliary body and low in the lens and aqueous humor, and in general, the Rabbit tissues had higher hydrolytic rates than the porcine ones. Esterase activity scaled to whole tissue was high in cornea and iris-ciliary body and low in aqueous humor and retinal pigment epithelium in both species. The current study revealed differences in esterase activities among the ocular tissues and the species. This basic knowledge on ocular esterases provides background information particularly for posterior segment drug development.Peer reviewe
