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Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical...

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Autores principales: Ichio, Atsushi, Sugimoto, Masahiko, Koike, Yuhki, Toiyama, Yuji, Kondo, Mineo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143914/
https://www.ncbi.nlm.nih.gov/pubmed/37109767
http://dx.doi.org/10.3390/medicina59040809
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author Ichio, Atsushi
Sugimoto, Masahiko
Koike, Yuhki
Toiyama, Yuji
Kondo, Mineo
author_facet Ichio, Atsushi
Sugimoto, Masahiko
Koike, Yuhki
Toiyama, Yuji
Kondo, Mineo
author_sort Ichio, Atsushi
collection PubMed
description Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 μg/μL of aflibercept (Af), or 25 μg/μL of bevacizumab (Be), or 10 μg/μL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.
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spelling pubmed-101439142023-04-29 Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice Ichio, Atsushi Sugimoto, Masahiko Koike, Yuhki Toiyama, Yuji Kondo, Mineo Medicina (Kaunas) Article Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 μg/μL of aflibercept (Af), or 25 μg/μL of bevacizumab (Be), or 10 μg/μL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety. MDPI 2023-04-21 /pmc/articles/PMC10143914/ /pubmed/37109767 http://dx.doi.org/10.3390/medicina59040809 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ichio, Atsushi
Sugimoto, Masahiko
Koike, Yuhki
Toiyama, Yuji
Kondo, Mineo
Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice
title Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice
title_full Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice
title_fullStr Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice
title_full_unstemmed Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice
title_short Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice
title_sort effects of topical or intravitreal application of anti-vascular endothelial growth factor on density of intestinal blood vessels of mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143914/
https://www.ncbi.nlm.nih.gov/pubmed/37109767
http://dx.doi.org/10.3390/medicina59040809
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