ArticleInvestigative ophthalmology & visual science2013
Intravitreal injection of TIMP3 or the EGFR inhibitor erlotinib offers protection from oxygen-induced retinopathy in mice.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Network Pharmacology Study on the Mechanisms ofApplied bionics and biomechanics · 2025Article
- Enhancing human capillary tube network assembly and maturation through upregulated expression of pericyte-derived TIMP-3.Frontiers in cell and developmental biology · 2024Article
- Tissue Inhibitor of Metalloproteases 3 (TIMP-3): In Vivo Analysis Underpins Its Role as a Master Regulator of Ectodomain Shedding.Membranes · 2022Review
- Tissue Inhibitor of Metalloproteinase-3 Ameliorates Diabetes-Induced Retinal Inflammation.Frontiers in physiology · 2021Article
- Long non-coding RNA RPSAP52 upregulates Timp3 by serving as the endogenous sponge of microRNA-365 in diabetic retinopathy.Experimental and therapeutic medicine · 2020Article
- MiR-221-3p regulates the microvascular dysfunction in diabetic retinopathy by targeting TIMP3.Pflugers Archiv : European journal of physiology · 2020Article
- miR-122 promotes diabetic retinopathy through targeting TIMP3.Animal cells and systems · 2020Article
- Role of Endothelial ADAM17 in Early Vascular Changes Associated with Diabetic Retinopathy.Journal of clinical medicine · 2020Article
- Tissue inhibitor of matrix metalloproteinase-3 has both anti-metastatic and anti-tumourigenic properties.Clinical & experimental metastasis · 2020Review
- Cigarette smoke-induced EGFR activation promotes epithelial mesenchymal migration of human retinal pigment epithelial cells through regulation of the FAK-mediated Syk/Src pathway.Molecular medicine reports · 2018Article
- Relationship between Pericytes and Endothelial Cells in Retinal Neovascularization: A Histological and Immunofluorescent Study of Retinal Angiogenesis.Korean journal of ophthalmology : KJO · 2018Article
- STAT3-mediated activation ofOncotarget · 2017Article
- TIMPs: versatile extracellular regulators in cancer.Nature reviews. Cancer · 2017Review
- S100A4 gene silencing in oxygen-induced ischemic retinopathy inhibits retinal neovascularization via down-regulation of CREB expression.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2016Article
- Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.Annual review of pharmacology and toxicology · 2016Article
- MicroRNA-410 reduces the expression of vascular endothelial growth factor and inhibits oxygen-induced retinal neovascularization.PloS one · 2014Article
- Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats.BMC genomics · 2014Article
- The epidermal growth factor receptor and its ligands in cardiovascular disease.International journal of molecular sciences · 2013Review
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11 authors at 6 institutions in 2 countries.
Funding
Abstract
purposePathological neovascularization is a crucial component of proliferative retinopathies. Previous studies showed that inactivation of A disintegrin and metalloproteinase 17 (ADAM17), a membrane-anchored metalloproteinase that regulates epidermal growth factor receptor (EGFR) signaling, reduces pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Here, we tested how genetic inactivation of a physiological ADAM17 inhibitor, the tissue inhibitor of matrix metalloproteinases-3 (TIMP3), or intravitreal injection of TIMP3 or of the EGFR inhibitor erlotinib influenced the outcome of OIR.
methodsWild-type mice were subjected to OIR in a chamber with 75% oxygen for 5 days beginning at postnatal day 7 (P7). Upon removal from the oxygen chamber at P12, they received a single intravitreal injection of TIMP3, erlotinib, or control. The central avascular area and neovascular tufts were measured after 5 days in room air (21% oxygen) at P17. Moreover, OIR experiments were performed with Timp3-/- mice and littermate controls.
resultsTimp3-/- mice showed greater revascularization of the central avascular area and developed equal or fewer neovascular tufts compared to littermate controls, depending on the genetic background. Wild-type mice injected with TIMP3 or erlotinib developed fewer neovascular tufts when compared to untreated littermates. Moreover, vessel regrowth into the avascular area was reduced in TIMP3-injected mice, but not in erlotinib-injected mice.
conclusionsThese studies demonstrate that TIMP3 and erlotinib inhibit pathological neovascularization in the mouse retina, most likely due to inactivation of ADAM17 and the EGFR, respectively. Thus, TIMP3 and erlotinib emerge as attractive candidate antiangiogenic compounds for prevention and treatment of proliferative retinopathies.
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