Abstract
Purpose :
To investigate the expression of Runx3 in murine retina, and the effects of RUNX3 overexpression on retinal neovascularization (RNV) in oxygen-induced retinopathy (OIR) mice, as well as to explore its effect on HIF1α-VEGF signaling pathway.
Methods :
Neonatal C57BL/6J mice were randomly divided into four groups: control (CON) group, OIR group, RUNX3-overexpression-OIR (RUNX3-AAV-OIR) group and vector-OIR (GFP-OIR) group. RUNX3-AAV-OIR group and GFP-OIR group were intravitreal injected with RUNX3-overexpressing adeno-associated virus (AAV) vectors and scramble vectors on P3, respectively. Neonatal mice of OIR group, RUNX3-AAV-OIR group and GFP-OIR group were exposed to 75% O2 for 5 days from P7 to P12, and then abruptly returned to room air. The size of neovascular area, avascular area, the number and morphology of tip cells were assessed and quantified by immunostaining in the flat-mounted retinas. The protein levels of HIF1α and VEGF in the retina were detected by Western blot.
Results :
RUNX3 mainly expressed in retinal vascular endothelium, and also in ganglial cell layer and inner nuclear layer of neonatal C57BL/6J mice on P17. Compared to OIR group, the size of retinal neovascular aera and avascular area, and the number of tip cells of RUNX3-AAV-OIR group decreased significantly, and the number and length of filopodia increased significantly, the elevated level of HIF1α and VEGF in the retina of OIR were significantly reduced by overexpressing the RUNX3 gene; while there were few changes of GFP-OIR group compared to OIR group.
Conclusions :
Overexpression of RUNX3 inhibited RNV as well as improved retinal vascular repair and remodeling of OIR, meanwhile decreased the expression levels of HIF1α and VEGF in OIR retina.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.