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  • Chemically Modified Heparin Reduces CNV

    By Lynda Seminara
    Selected by Prem S. Subramanian, MD, PhD
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    Journal Highlights

    Graefe’s Archive for Clinical and Experimental Ophthalmology
    Published online Sept. 13, 2022

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    Developing drugs to target the angio­genic cascade of choroidal neovascu­larization (CNV) may improve the life of patients with age-related macular degeneration (AMD). Although hep­arin is known for its antiangiogenic and anti-inflammatory properties, it has potent anticoagulant activity that may limit clinical utility. Chemically modified forms of heparin, based on deleting N- and O-sulfated groups from the structure, can maintain the drug’s antiangiogenic potential while limiting interference with hemostasis. Previously, Kniggendorf et al. observed that a heparinoid with low content of 2-O-sulfate groups, isolated from marine shrimp, had negligible antico­agulant and hemorrhagic activities but still reduced acute inflammation and angiogenetic processes. For this study, they explored the effects of a chemically modified heparin. They confirmed that it has potent antiangiogenic, -prolif­erative, and -migratory effects with virtually no anticoagulant action or retinal cytotoxicity.

    The compound they tested was N-desulfated Re–N-acetylated hepa­rin. In vitro assays included cell tube formation, viability, proliferation, and migration. Endothelial cells (EC) were counted after 24 hours of treatment with the modified heparin (10, 100, or 1,000 ng/mL) or balanced saline solu­tion (BSS; controls). In vivo assessment was performed after laser induction of CNV in rats, followed by a 5-μL intra­vitreal injection of modified heparin (100, 1,000, or 10,000 ng/mL) or BSS. After 14 days, the CNV underwent immunofluorescence analysis.

    Relative to BSS controls, the modi­fied heparin significantly reduced cell proliferation, tube formation, and mi­gration, but it did not alter cell viability. Within 24 hours of in vitro treatment, all quantities of the heparin solution significantly inhibited EC proliferation (p = .0011); the higher dose was signifi­cantly more effective than either of the lower doses (p < .05). In vivo interven­tion yielded mean CNV measurements that were significantly smaller (p = .0065) with modified heparin: 54.84 × 106 pix­els/mm with 100 ng/mL, 58.77 × 106 pixels/mm with 1,000 ng/mL, and 59.42 × 106 pixels/mm with 10,000 ng/mL. The mean CNV area in the control group was 72.23 × 106 pixels/mm. Mean perimeter values also were significantly better with the heparin solution (p = .0235).

    Based on the findings, the authors believe that this form of heparin may be a candidate for treatment of neovas­cular AMD and other angioprolifera­tive diseases.

    The original article can be found here.