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J.-J. You, C.-H. Yang, C.-M. Yang, M.-S. Chen; Cysteine-Rich 61, Ccn1, as a Mediator of Ocular Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3449.
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Cysteine-rich 61 (Cyr61) is a angiogenic factor. It is not clear that Cyr61 plays in ocular angiogenesis. We investigate Cyr61-mediated angiogenesis in vitro and in vivo to understand its role in ocular angiogenic disorders.
Cyr61 effects on monkey choroidal retinal endothelial cell (RF/6A) was evaluated with proliferative, chemotaxis assay and Matrigel capillary tube formation assay in vitro. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to detect mRNA and protein expression of Cyr61 in RF/6A cells under hypoxic condition. Oxygen-induced retinopathy model of mice (OIR) was used to test the angiogenic property of Cyr61 in vivo. Cyr61 levels of vitreous samples from proliferative diabetic retinopathy (PDR) patients were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Immunodepletion of Cyr61 in PDR vitreous samples by anti-Cyr61 monoclonal antibody was observed in endothelial cells chemotaxis assays.
Cyr61 significantly induced proliferation and migration of RF/6A. Cyr61 induced formation of endothelial cell capillary tubes on Matrigel. Expression of Cyr61 was detected in RF/6A by RT-PCR and Western blotting under hypoxic condition. Cyr61 significantly expressed on new vessels in the mice of the OIR model. Intravitreal injection of anti-mouse Cyr61 antibody decreased retinal angiogenesis in the OIR model. Vitreous level of Cyr61 was elevated in PDR patients as compared to control. Immunodepletion of Cyr61 from PDR vitreous samples caused 50.5 +8.0% less migration of RF/6A.
Cyr61 is an angiogenic mediator in vitro and in vivo. Hypoxia could induce expression of Cyr61. Vitreous level of Cyr61 was elevated in PDR patients. Cyr61 may play an important role in ocular angiogenic disorders such as PDR.
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