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Xi Lu, Yue Xu, Xiaoling Liang; RUNX3 regulates PHD2-HIF1α-VEGF signal axis and plays a vital role in the retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3263. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
RUNX3 has been demonstrated to inhibit angiogenesis by modulating PHD2-HIF1α-VEGF signal axis in tumor. This study was to investigate the effect of RUNX3 on retinal neovascularization (RNV) and its mechanism.
A transgenic mouse model with conditional loss of RUNX3 in retina was generated. Normal retinal vascular development as well as progression and severity of RNV in oxygen-induced retinopathy (OIR) models was observed both in normal C57BL/6J and RUNX3 conditional knock-out (RUNX3-cKO) mice. Further, the interaction between RUNX3 and PHD2, HIF1α was detected in mouse retinal microvascular epithelial cells (mRMECs) under different oxygen condition by co-immunoprecipitation.
RUNX3 deficiency led to aberrant angiogenesis in the developing murine retina. The size of retinal neovascular area, the number of filopodia of tip cells and the number of pre-retinal neovascular cell nuclei were significantly increased RUNX3-cKO OIR mice, while the size of retinal neovascular area was reduced (#P<0.05, ##P<0.01, ###P<0.001). Next, the results of co-immunoprecipitation showed that RUNX3 had an interaction with PHD2 and HIF1α in mRMECs under normal culture condition, which was weaken under hypoxic condition (*P<0.05, **P<0.01, ***P<0.001).
Our results indicated that RUNX3 play a pivotal role during retinal vascular development as well as in the progression of RNV. Its effects on RNV might be realized by regulation of PHD2-HIF1α-VEGF signal axis. This might provide a novel target for RNV therapeutic strategy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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