期刊
JCI INSIGHT
卷 3, 期 19, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.99448
关键词
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资金
- Herman Svensson Foundation
- Cronqvists Foundation
- Linnea and Josef Carlssons Foundation
- HKH Kronprinsessan Lovisas forening for barnasjukvard/Stiftelsen Axel Tielmans Minnesfond
- Stiftelsen Kronprinsessan Margaretas Arbetsnamnd for synskadade
- De blindas vanner NIH [EY024864, EY017017, P01 HD18655, P01 HL046925, HL69990]
- European Commission FP7 project [305485 PREVENT-ROP]
- Lowy Medical Research Institute
- Deutsche Forschungsgemeinschaft (DFG) [CA 1940/1-1]
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 x 10(9)/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.
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