Therapeutic effects of topical Netrin-4 inhibits corneal neovascularization in alkali-burn rats

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Abstract

© 2015 Han et al. Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an antiangiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to al-kali- burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin- 4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues.

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Han, Y., Shao, Y., Liu, T., Qu, Y. L., Li, W., & Liu, Z. (2015). Therapeutic effects of topical Netrin-4 inhibits corneal neovascularization in alkali-burn rats. PLoS ONE, 10(4). https://doi.org/10.1371/journal.pone.0122951

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