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Aflibercept clearance through the drainage system in a rat model

BACKGROUND: As intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat mod...

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Autores principales: Keshet, Yariv, Gal-Or, Orly, Schaap Fogler, Michal, Mimouni, Karin, Ben Ishai, Meydan, Weinberger, Dov, Dotan, Assaf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427964/
https://www.ncbi.nlm.nih.gov/pubmed/34496977
http://dx.doi.org/10.1186/s40942-021-00322-8
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author Keshet, Yariv
Gal-Or, Orly
Schaap Fogler, Michal
Mimouni, Karin
Ben Ishai, Meydan
Weinberger, Dov
Dotan, Assaf
author_facet Keshet, Yariv
Gal-Or, Orly
Schaap Fogler, Michal
Mimouni, Karin
Ben Ishai, Meydan
Weinberger, Dov
Dotan, Assaf
author_sort Keshet, Yariv
collection PubMed
description BACKGROUND: As intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat model, to test if an aggregation exists. METHODS: Choroidal neovascular lesions (CNV) were induced in the right eye of 12 brown Norway rats, using indirect laser ophthalmoscope. Intravitreal Aflibercept injection (0.12 mg/3 µl) was performed 3 days after CNV induction. Rats were euthanized at predetermine time intervals of 3, 6, 24 and 48 h post injection, with immediate enucleation for histological analysis with H&E and immunofluorescence staining. Aflibercept molecules were stained with red fluorescence thanks to the formation of the immune complex Aflibercept-Rabbit anti human IgG-Anti rabbit antibodies-Cy3. RESULTS: Immediately after the injection, a strong fluorescence signal was detected, indicating the presence of Aflibercept in the iridocorneal angle. At 3- and 6-h interval a strong signal of Aflibercept was still seen. Six hours post injection, the signal was highly concentrated in Schlemm’s canal. In the 2 eyes harvested 24 h post Aflibercept injection, red fluorescence signal intensity was decreased in one eye, occupying mainly intra scleral venous plexuses, and absent in the other eye. At 48 h there was no fluorescence signal, confirming complete clearance of Aflibercept. CONCLUSIONS: In our rat model, a complete clearance of Aflibercept from the anterior chamber angle, was seen 48 h after the injection. This finding refutes the theory of possible connection between IOP elevation and mechanical obstruction. Evacuation time of Aflibercept through the angle is of the same magnitude as that of Bevacizumab in the same rat model.
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spelling pubmed-84279642021-09-10 Aflibercept clearance through the drainage system in a rat model Keshet, Yariv Gal-Or, Orly Schaap Fogler, Michal Mimouni, Karin Ben Ishai, Meydan Weinberger, Dov Dotan, Assaf Int J Retina Vitreous Original Article BACKGROUND: As intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat model, to test if an aggregation exists. METHODS: Choroidal neovascular lesions (CNV) were induced in the right eye of 12 brown Norway rats, using indirect laser ophthalmoscope. Intravitreal Aflibercept injection (0.12 mg/3 µl) was performed 3 days after CNV induction. Rats were euthanized at predetermine time intervals of 3, 6, 24 and 48 h post injection, with immediate enucleation for histological analysis with H&E and immunofluorescence staining. Aflibercept molecules were stained with red fluorescence thanks to the formation of the immune complex Aflibercept-Rabbit anti human IgG-Anti rabbit antibodies-Cy3. RESULTS: Immediately after the injection, a strong fluorescence signal was detected, indicating the presence of Aflibercept in the iridocorneal angle. At 3- and 6-h interval a strong signal of Aflibercept was still seen. Six hours post injection, the signal was highly concentrated in Schlemm’s canal. In the 2 eyes harvested 24 h post Aflibercept injection, red fluorescence signal intensity was decreased in one eye, occupying mainly intra scleral venous plexuses, and absent in the other eye. At 48 h there was no fluorescence signal, confirming complete clearance of Aflibercept. CONCLUSIONS: In our rat model, a complete clearance of Aflibercept from the anterior chamber angle, was seen 48 h after the injection. This finding refutes the theory of possible connection between IOP elevation and mechanical obstruction. Evacuation time of Aflibercept through the angle is of the same magnitude as that of Bevacizumab in the same rat model. BioMed Central 2021-09-08 /pmc/articles/PMC8427964/ /pubmed/34496977 http://dx.doi.org/10.1186/s40942-021-00322-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Original Article
Keshet, Yariv
Gal-Or, Orly
Schaap Fogler, Michal
Mimouni, Karin
Ben Ishai, Meydan
Weinberger, Dov
Dotan, Assaf
Aflibercept clearance through the drainage system in a rat model
title Aflibercept clearance through the drainage system in a rat model
title_full Aflibercept clearance through the drainage system in a rat model
title_fullStr Aflibercept clearance through the drainage system in a rat model
title_full_unstemmed Aflibercept clearance through the drainage system in a rat model
title_short Aflibercept clearance through the drainage system in a rat model
title_sort aflibercept clearance through the drainage system in a rat model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427964/
https://www.ncbi.nlm.nih.gov/pubmed/34496977
http://dx.doi.org/10.1186/s40942-021-00322-8
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