ArticleScience advances2023
Thrombospondin-1 proteomimetic polymers exhibit anti-angiogenic activity in a neovascular age-related macular degeneration mouse model.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Intravitreal Dexamethasone Implant in Retinal Vein Occlusion: A Pilot Study Exploring Baseline Ocular and Circulating Biomarkers.International journal of molecular sciences · 2026Article
- Mechanism of EC-EXOs-Derived THBS3 Targeting CD47 to Regulate BMSCs Differentiation to Ameliorate Bone Loss.Cell proliferation · 2025Article
- Adrb2 Expression in Ocular-Infiltrating Macrophages Is Necessary for Interleukin-6 Expression and Choroidal Neovascularization.Investigative ophthalmology & visual science · 2025Article
- Proteomimetic polymer blocks mitochondrial damage, rescues Huntington's neurons, and slows onset of neuropathology in vivo.Science advances · 2024Article
- Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.International journal of experimental pathology · 2024Review
- Tissue-engineered mesenchymal stem cell constructs alleviate tendinopathy by suppressing vascularization.Bioactive materials · 2024Article
- Connective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery.International journal of molecular sciences · 2024Review
- Bioengineering strategies targeting angiogenesis: Innovative solutions for osteonecrosis of the femoral head.Journal of tissue engineeringReview
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the developed world. Current therapy includes monthly intraocular injections of anti-VEGF antibodies, which are ineffective in up to one third of patients. Thrombospondin-1 (TSP1) inhibits angiogenesis via CD36 binding, and its down-regulated expression is negatively associated with the onset of nAMD. Here, we describe TSP1 mimetic protein-like polymers (TSP1 PLPs). TSP1 PLPs bind CD36 with high affinity, resist degradation, show prolonged intraocular half-lives (13.1 hours), have no toxicity at relevant concentrations in vivo (40 μM), and are more efficacious in ex vivo choroidal sprouting assays compared to the peptide sequence and Eylea (aflibercept), the current standard of care anti-VEGF treatment. Furthermore, PLPs exhibit superior in vivo efficacy in a mouse model for nAMD compared to control PLPs consisting of scrambled peptide sequences, using fluorescein angiography and immunofluorescence. Since TSP-1 inhibits angiogenesis by VEGF-dependent and independent mechanisms, TSP1 PLPs are a potential therapeutic for patients with anti-VEGF treatment-resistant nAMD.
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