Autor(es)

Grupenmacher, Alex Treiger ; Augusto, Bianca Oliveira ; Fetter, Bruna Zancanelli ; Rocha, Juliana P. ; Araujo, Diego Lisboa ; Kniggendorf, Vinicius ; Nader, Helena B. ; Regatieri, Caio Vinicius Saito ; Dreyfuss, Juliana L.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 26, n. 16, p. 21-pg., 2025-08-08.

Resumo

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide, primarily due to pathological choroidal neovascularization (CNV). Our study investigates a chemically modified heparin derivative as a novel strategy to selectively modulate angiogenic signaling, offering a reduced anticoagulant risk and preclinical support for AMD treatment. We explored the therapeutic potential of 6-O-desulfated heparin (Hep-6Od) as an antiangiogenic agent with diminished anticoagulant activity. Synthesized via selective 6-O-desulfation and characterized using nuclear magnetic resonance (NMR), Hep-6Od demonstrated safety in retinal pigment epithelial cells with no cytotoxic effects at various concentrations. In vitro, the compound significantly inhibited endothelial cell proliferation, migration, and capillary tube formation. Differential scanning fluorimetry (DSF) assays confirmed molecular interaction between Hep-6Od and fibroblast growth factor 2 (FGF-2), suggesting interference with pro-angiogenic signaling pathways. In vivo, a laser-induced CNV model in lean Zucker rats showed a dose-dependent reduction in neovascular lesion areas after an intravitreal Hep-6Od injection. Compared to unfractionated heparin, Hep-6Od exhibited reduced anticoagulant effects in PT and aPTT assays while maintaining robust antiangiogenic properties. These findings support Hep-6Od as a promising alternative to anti-vascular endothelial growth factor (VEGF) therapies for AMD treatment, potentially expanding current retinal vascular disease interventions. The results underscore its potential to transform AMD management, pending further clinical validation and awaiting confirmation in further studies. (AU)

• Processo FAPESP: 23/07464-4 - Glicosaminoglicanos na interação célula matriz extracelular - uma abordagem translacional
• Beneficiário: Helena Bonciani Nader
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/03964-6 - Glicosaminoglicanos e Proteoglicanos: Relação Estrutura e Função
• Beneficiário: Helena Bonciani Nader
• Modalidade de apoio: Auxílio à Pesquisa - Temático