| Literature DB >> 30282834 |
Bertan Cakir1,2, Raffael Liegl1,3, Gunnel Hellgren4, Pia Lundgren4, Ye Sun1, Susanna Klevebro5, Chatarina Löfqvist4, Clara Mannheimer4, Steve Cho1, Alexander Poblete1, Rubi Duran1, Boubou Hallberg5, Jorge Canas6, Viola Lorenz6, Zhi-Jian Liu6, Martha C Sola-Visner6, Lois Eh Smith1, Ann Hellström4.
Abstract
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.Entities:
Keywords: Angiogenesis; Platelets; Retinopathy; Vascular Biology
Year: 2018 PMID: 30282834 PMCID: PMC6237470 DOI: 10.1172/jci.insight.99448
Source DB: PubMed Journal: JCI Insight ISSN: 2379-3708