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Graefe's Archive for Clinical and Experimental Ophthalmology

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13-09-2022 | Anticoagulant | Basic Science

New anti-angiogenic compound based on chemically modified heparin

Authors: Vinicius Kniggendorf, Maria Eduarda Perrud Souza, Thatiane Russo, Marcelo Andrade de Lima, Alex Treiger Grupenmacher, Caio V. Regatieri, Juliana L. Dreyfuss

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 12/2022

Abstract

Purpose

The purpose of this study was to measure the anti-angiogenic effect of N-desulfated Re–N-acetylated, a chemically modified heparin (mHep).

Methods

In vitro assays (cell tube formation, viability, proliferation, and migration) with endothelial cells were performed after 24 h of treatment with mHep at 10, 100, and 1000 ng/mL or saline. In vivo tests were performed after laser-induced choroidal neovascularization (CNV) in rats, followed by an intravitreal injection (5 µL) of mHep (10, 100, 1000 ng/mL) or balanced salt solution. Immunofluorescence analysis of the CNV was performed after 14 days.

Results

mHep produced a statistically significant reduction in cell proliferation, tube formation, and migration, without cell viability changes when compared to saline. Mean measures of CNV area were 54.84 × 10⁶ pixels/mm (± 12.41 × 10⁶), 58.77 × 10⁶ pixels/mm (± 17.52 × 10⁶), and 59.42 × 10⁶ pixels/mm (± 17.33 × 10⁶) in groups 100, 1000, and 10,000 ng/mL, respectively, while in the control group, mean area was 72.23 × 10⁶ (± 16.51 × 10⁶). The P value was 0.0065. Perimeter analysis also demonstrated statistical significance (P = 0.0235) with the mean measure of 93.55 × 10⁴, 94.23 × 10⁴, and 102 × 10⁴ in the 100 ng/mL, 1000 ng/mL, and control groups, respectively.

Conclusions

These results suggest that mHep N-DRN is a potent anti‐angiogenic, anti‐proliferative, and anti-migratory compound with negligible anticoagulant or hemorrhagic action and no cytotoxicity for retina cells. This compound may serve as a candidate for treating choroidal neovascularization.

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Title: New anti-angiogenic compound based on chemically modified heparin
Authors: Vinicius Kniggendorf
Maria Eduarda Perrud Souza
Thatiane Russo
Marcelo Andrade de Lima
Alex Treiger Grupenmacher
Caio V. Regatieri
Juliana L. Dreyfuss
Publication date: 13-09-2022
Publisher: Springer Berlin Heidelberg
Keywords: Anticoagulant
Heparin
Laser
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 12/2022
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-022-05828-x

2024 ASCO Annual Meeting

Springer Medicine

New anti-angiogenic compound based on chemically modified heparin

Abstract

Purpose

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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