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Lingjia Liu, Takeshi Nakao, Reza Dana, Jia Yin; Role of Substance P in Promoting Corneal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):950. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Substance P (SP) is a key regulator of inflammation and wound healing, and its effects are mainly mediated via neurokinin receptor 1 (NK1R). The aim of this study is to investigate the role of SP in corneal neovascularizaion (KNV) using vascular endothelial cell culture (MS-1 cell line) in vitro and suture-induced KNV mouse model in vivo.
Vascular endothelial cells (VEC) were treated with 1μmol SP and then cultured for 24 hours. Cell proliferation using BrdU Incorporation assay and tube formation were assessed. KNV was induced by intra-stromal suture placement in BALB/C mice. Topical application of NK1R antagonist Spantide I (three times a day, daily) was applied after suture placement, PBS served as control. Corneal opacity and neovascularization were monitored. After 14 days, the vascularized area was photographed and quantified by double-blind analysis. Corneal opacity also was assessed by photographs. Corneal hem- and lymph-angiogenesis was assessed using immunostaining with CD31 and LYVE1 antibodies, respectively.
SP significantly increased VEC proliferation (+50%, p<0.001). In tube formation assay, both tube length (5.2-fold increase, p=0.001) and number of tube junctions (3.3-fold increase, p=0.003) were significantly increased in the presence of SP. Compared with control group, Spantide I treatment resulted in a significant decrease in vascularized area (85.4%±8.2 in control vs. 66.4%±16.0 in Spantide Ι, P=0.03). Corneal opacity was comparable between control and Spantide Ι groups.
Our results suggest that exogenous SP promotes the proliferation and tube formation of vascular endothelial cells in vitro, demonstrating its pro-angiogenic property. Moreover, blockade of SP-NK1R signaling with Spantide I significantly reduces corneal neovascularization in vivo.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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