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Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage

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Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage. / Thaler, Sebastian; Fiedorowicz, Michal; Choragiewicz, Tomasz J; Bolz, Sylvia; Tura, Ayseguel; Henke-Fahle, Sigrid; Yoeruek, Efdal; Zrenner, Eberhart; Bartz-Schmidt, Karl-Ulrich; Ziemssen, Focke; Schuettauf, Frank.

In: ACTA OPHTHALMOL, Vol. 88, No. 5, 08.2010, p. e170-6.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Thaler, S, Fiedorowicz, M, Choragiewicz, TJ, Bolz, S, Tura, A, Henke-Fahle, S, Yoeruek, E, Zrenner, E, Bartz-Schmidt, K-U, Ziemssen, F & Schuettauf, F 2010, 'Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage', ACTA OPHTHALMOL, vol. 88, no. 5, pp. e170-6. https://doi.org/10.1111/j.1755-3768.2010.01927.x

APA

Thaler, S., Fiedorowicz, M., Choragiewicz, T. J., Bolz, S., Tura, A., Henke-Fahle, S., Yoeruek, E., Zrenner, E., Bartz-Schmidt, K-U., Ziemssen, F., & Schuettauf, F. (2010). Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage. ACTA OPHTHALMOL, 88(5), e170-6. https://doi.org/10.1111/j.1755-3768.2010.01927.x

Vancouver

Thaler S, Fiedorowicz M, Choragiewicz TJ, Bolz S, Tura A, Henke-Fahle S et al. Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage. ACTA OPHTHALMOL. 2010 Aug;88(5):e170-6. https://doi.org/10.1111/j.1755-3768.2010.01927.x

Bibtex

@article{551e9cdae055434a8f0f2d0a827273a9,
title = "Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage",
abstract = "PURPOSE: To evaluate the effects of intravitreally introduced vascular endothelial growth factor (VEGF) inhibitors in rat eyes with healthy retinal ganglion cells (RGC) and into others with N-methyl-D-aspartate (NMDA)-induced RGC damage.METHODS: Bevacizumab, ranibizumab and pegaptanib were intravitreally injected each at two different concentrations. Respective vehicles of the three substances served as controls. In a different group, additionally a rat anti-VEGF antibody was injected after NMDA treatment. Retrogradely labelled RGC were counted on retinal wholemounts 1 week or 2 months after intravitreal introduction of the VEGF inhibitors. Electron microscopy (EM) was performed on normal rat eyes 2 months after introduction of the VEGF inhibitors.RESULTS: RGC counts in healthy rat eyes were essentially unchanged from those of the control animals after the administration of both low and high concentrations of bevacizumab, ranibizumab or pegaptanib. Compared to the other two substances, however, high doses of pegaptanib and its respective vehicle significantly decreased RGC after 1 week and led to a marked increase of mitochondrial swelling in EM. In eyes with NMDA-induced RGC damage, no changes of RGC numbers were detected after rat anti-VEGF antibody or bevacizumab, ranibizumab and pegaptanib at both tested concentrations.CONCLUSIONS: Even at higher doses, bevacizumab and ranibizumab showed no toxic effects on RGC in vivo in either untreated rats or in the NMDA-induced RGC damage model. Also a rat anti-VEGF antibody showed no adverse effects after NMDA. Anti-VEGF therapy therefore appears safe even for eyes with additional excitotoxic RGC damage. Potential harm from the pegaptanib carrier solution at very high local concentrations cannot be excluded.",
keywords = "Angiogenesis Inhibitors/toxicity, Animals, Antibodies, Monoclonal/toxicity, Antibodies, Monoclonal, Humanized, Aptamers, Nucleotide/toxicity, Bevacizumab, Cell Count, Excitatory Amino Acid Agonists/toxicity, Female, Injections, Mitochondria/drug effects, N-Methylaspartate/toxicity, Ranibizumab, Rats, Rats, Inbred BN, Retinal Ganglion Cells/drug effects, Vascular Endothelial Growth Factor A/antagonists & inhibitors, Vitreous Body",
author = "Sebastian Thaler and Michal Fiedorowicz and Choragiewicz, {Tomasz J} and Sylvia Bolz and Ayseguel Tura and Sigrid Henke-Fahle and Efdal Yoeruek and Eberhart Zrenner and Karl-Ulrich Bartz-Schmidt and Focke Ziemssen and Frank Schuettauf",
year = "2010",
month = aug,
doi = "10.1111/j.1755-3768.2010.01927.x",
language = "English",
volume = "88",
pages = "e170--6",
journal = "ACTA OPHTHALMOL",
issn = "1755-375X",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage

AU - Thaler, Sebastian

AU - Fiedorowicz, Michal

AU - Choragiewicz, Tomasz J

AU - Bolz, Sylvia

AU - Tura, Ayseguel

AU - Henke-Fahle, Sigrid

AU - Yoeruek, Efdal

AU - Zrenner, Eberhart

AU - Bartz-Schmidt, Karl-Ulrich

AU - Ziemssen, Focke

AU - Schuettauf, Frank

PY - 2010/8

Y1 - 2010/8

N2 - PURPOSE: To evaluate the effects of intravitreally introduced vascular endothelial growth factor (VEGF) inhibitors in rat eyes with healthy retinal ganglion cells (RGC) and into others with N-methyl-D-aspartate (NMDA)-induced RGC damage.METHODS: Bevacizumab, ranibizumab and pegaptanib were intravitreally injected each at two different concentrations. Respective vehicles of the three substances served as controls. In a different group, additionally a rat anti-VEGF antibody was injected after NMDA treatment. Retrogradely labelled RGC were counted on retinal wholemounts 1 week or 2 months after intravitreal introduction of the VEGF inhibitors. Electron microscopy (EM) was performed on normal rat eyes 2 months after introduction of the VEGF inhibitors.RESULTS: RGC counts in healthy rat eyes were essentially unchanged from those of the control animals after the administration of both low and high concentrations of bevacizumab, ranibizumab or pegaptanib. Compared to the other two substances, however, high doses of pegaptanib and its respective vehicle significantly decreased RGC after 1 week and led to a marked increase of mitochondrial swelling in EM. In eyes with NMDA-induced RGC damage, no changes of RGC numbers were detected after rat anti-VEGF antibody or bevacizumab, ranibizumab and pegaptanib at both tested concentrations.CONCLUSIONS: Even at higher doses, bevacizumab and ranibizumab showed no toxic effects on RGC in vivo in either untreated rats or in the NMDA-induced RGC damage model. Also a rat anti-VEGF antibody showed no adverse effects after NMDA. Anti-VEGF therapy therefore appears safe even for eyes with additional excitotoxic RGC damage. Potential harm from the pegaptanib carrier solution at very high local concentrations cannot be excluded.

AB - PURPOSE: To evaluate the effects of intravitreally introduced vascular endothelial growth factor (VEGF) inhibitors in rat eyes with healthy retinal ganglion cells (RGC) and into others with N-methyl-D-aspartate (NMDA)-induced RGC damage.METHODS: Bevacizumab, ranibizumab and pegaptanib were intravitreally injected each at two different concentrations. Respective vehicles of the three substances served as controls. In a different group, additionally a rat anti-VEGF antibody was injected after NMDA treatment. Retrogradely labelled RGC were counted on retinal wholemounts 1 week or 2 months after intravitreal introduction of the VEGF inhibitors. Electron microscopy (EM) was performed on normal rat eyes 2 months after introduction of the VEGF inhibitors.RESULTS: RGC counts in healthy rat eyes were essentially unchanged from those of the control animals after the administration of both low and high concentrations of bevacizumab, ranibizumab or pegaptanib. Compared to the other two substances, however, high doses of pegaptanib and its respective vehicle significantly decreased RGC after 1 week and led to a marked increase of mitochondrial swelling in EM. In eyes with NMDA-induced RGC damage, no changes of RGC numbers were detected after rat anti-VEGF antibody or bevacizumab, ranibizumab and pegaptanib at both tested concentrations.CONCLUSIONS: Even at higher doses, bevacizumab and ranibizumab showed no toxic effects on RGC in vivo in either untreated rats or in the NMDA-induced RGC damage model. Also a rat anti-VEGF antibody showed no adverse effects after NMDA. Anti-VEGF therapy therefore appears safe even for eyes with additional excitotoxic RGC damage. Potential harm from the pegaptanib carrier solution at very high local concentrations cannot be excluded.

KW - Angiogenesis Inhibitors/toxicity

KW - Animals

KW - Antibodies, Monoclonal/toxicity

KW - Antibodies, Monoclonal, Humanized

KW - Aptamers, Nucleotide/toxicity

KW - Bevacizumab

KW - Cell Count

KW - Excitatory Amino Acid Agonists/toxicity

KW - Female

KW - Injections

KW - Mitochondria/drug effects

KW - N-Methylaspartate/toxicity

KW - Ranibizumab

KW - Rats

KW - Rats, Inbred BN

KW - Retinal Ganglion Cells/drug effects

KW - Vascular Endothelial Growth Factor A/antagonists & inhibitors

KW - Vitreous Body

U2 - 10.1111/j.1755-3768.2010.01927.x

DO - 10.1111/j.1755-3768.2010.01927.x

M3 - SCORING: Journal article

C2 - 20491691

VL - 88

SP - e170-6

JO - ACTA OPHTHALMOL

JF - ACTA OPHTHALMOL

SN - 1755-375X

IS - 5

ER -