Song Yong-Seok, Wang Shoujian, Inampudi Samay, Risa Hope, Sorenson Christine M, Sheibani Nader
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
Cells. 2025 Sep 21;14(18):1473. doi: 10.3390/cells14181473.
Pericytes produce vascular endothelial growth factor-A (VEGF-A; hereafter referred to as VEGF). VEGF inhibits pericyte proliferation and migration through enhanced VEGFR2 and PDGFRβ heterodimerization. Heterodimerization of these receptors on perivascular supporting cells, mediated by VEGF in culture, mitigates signaling through these receptors and promotes a quiescent phenotype. However, the detailed cellular mechanisms and the significance of these interactions in vivo require further investigation. The cell-autonomous activities of pericyte VEGF expression during vascular development and neovascularization remain unknown. Here we utilized mice conditionally lacking in pericytes () to examine its impact on retinal vascular development and pathological ocular neovascularization. Vascular integrity was also assessed in older mice using fundus imaging and fluorescein angiography. The lack of pericyte expression delayed the initial spreading of the superficial layer of the retinal vasculature. Mice lacking pericyte expression had similar numbers of retinal endothelial cells and arteries to their wild-type littermates. However, the number of pericytes was significantly reduced in younger mice but increased in more mature mice. In addition, pericyte deficiency did not impact responses during oxygen-induced ischemic retinopathy and laser-induced choroidal neovascularization. Thus, pericyte VEGF expression plays a role during early stages of retinal vascular development with limited influence on mature retinal vascularization, its integrity, and neovascularization.
周细胞产生血管内皮生长因子 -A（VEGF -A；以下简称VEGF）。VEGF通过增强VEGFR2和PDGFRβ异二聚化来抑制周细胞增殖和迁移。在培养中由VEGF介导的血管周围支持细胞上这些受体的异二聚化减轻了通过这些受体的信号传导，并促进静止表型。然而，这些相互作用在体内的详细细胞机制及其意义仍需进一步研究。血管发育和新生血管形成过程中周细胞VEGF表达的细胞自主活性仍然未知。在这里，我们利用条件性缺乏周细胞的小鼠来检查其对视网膜血管发育和病理性眼部新生血管形成的影响。还使用眼底成像和荧光素血管造影术对老年小鼠的血管完整性进行了评估。周细胞表达的缺失延迟了视网膜血管系统表层的初始扩展。缺乏周细胞表达的小鼠与其野生型同窝仔相比，视网膜内皮细胞和动脉数量相似。然而，在年轻小鼠中周细胞数量显著减少，但在更成熟的小鼠中增加。此外，周细胞缺陷对氧诱导的缺血性视网膜病变和激光诱导的脉络膜新生血管形成过程中的反应没有影响。因此，周细胞VEGF表达在视网膜血管发育的早期阶段起作用，对成熟视网膜血管化、其完整性和新生血管形成的影响有限。
