Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Germany.
JCI Insight. 2018 Oct 4;3(19):99448. doi: 10.1172/jci.insight.99448.
Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (<100 × 109/l) at ≥30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
早产儿视网膜病变(ROP)的特征是血管丢失后视网膜新生血管异常。血小板调节血管生成,可能影响 ROP 的进展。在早产儿中,我们评估了 ROP 并与纵向产后血小板计数相关(n = 202)。在胎龄≥30 周(ROP 开始时)≥100×109/L 的任何血小板减少症发作均与需要治疗的严重 ROP 独立相关。与 ROP 严重程度较轻的婴儿相比,患有严重 ROP 的婴儿每周血小板中位数也较低。在 ROP 的氧诱导的小鼠视网膜病变模型中,P17(新生血管化高峰期)的血小板计数低于对照组。P15 和 P16 的血小板输注抑制了新生血管形成,血小板耗竭增加了新生血管形成。血小板输注降低了视网膜血管内皮生长因子 A(VEGFA)mRNA 和蛋白表达;血小板耗竭增加了视网膜 VEGFA mRNA 和蛋白表达。具有完整颗粒的静止血小板减少了新生血管形成,而激活的血小板脱颗粒则没有。这些数据表明,血小板释放物对内皮细胞具有局部抗血管生成作用,从而在下游抑制神经视网膜中的 VEGFA。ROP 新生血管形成期的血小板计数低与早产儿严重 ROP 的发生显著相关。在视网膜病变的小鼠模型中,新生血管形成期的血小板输注抑制了视网膜病变。