The development of the retinal vasculature is essential to maintain health of the tissue, but the developmental mechanisms are not completely understood. The aim of this study was to investigate the cell-autonomous role of retinoic acid signaling in endothelial cells during retina vascular development. Using a temporal and cell-specific mouse model to disrupt retinoic acid signaling in endothelial cells in the postnatal retina (Pdgfb^icre/+ dnRAR403^fl/fl mutants), we discovered that angiogenesis in the retina is significantly decreased with a reduction in retina vascularization, endothelial tip cell number and filipodia, and endothelial ‘crowding’ of stalk cells. Interestingly, by P15, the vasculature can overcome the early angiogenic defect and fully vascularized the retina. At P60, the vasculature is intact with no evidence of retina cell death or altered blood retinal barrier integrity. Further, we identified that the angiogenic defect seen in mutants at P6 correlates with decreased Vegfr3 expression in endothelial cells. Collectively, our work identified a previously unappreciated function for endothelial retinoic acid signaling in early retinal angiogenesis.

视网膜血管的发育对于维持组织的健康至关重要，但其发育机制尚不完全清楚。本研究的目的是研究视黄酸信号在视网膜血管发育过程中在内皮细胞中的细胞自主作用。使用时间和细胞特异性小鼠模型破坏出生后视网膜内皮细胞中的视黄酸信号（Pdgfb ^icre/+ dnRAR403 ^fl/fl突变体），我们发现随着视网膜血管形成、内皮尖端细胞数量和丝状伪足以及内皮细胞“拥挤”的减少，视网膜中的血管生成显着减少。有趣的是，到 P15，脉管系统可以克服早期血管生成缺陷并使视网膜完全血管化。在 P60，脉管系统完好无损，没有视网膜细胞死亡或血视网膜屏障完整性改变的证据。此外，我们发现在 P6 突变体中观察到的血管生成缺陷与内皮细胞中Vegfr3表达降低相关。总的来说，我们的工作确定了早期视网膜血管生成中内皮视黄酸信号传导的一个以前未被重视的功能。