Retinal hypoxia and angiogenesis with methamphetamine.

Retinal hypoxia and angiogenesis with methamphetamine.
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DOI:
10.1016/j.exer.2021.108540
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发表时间:
2021-05
影响因子:
3.4
通讯作者:
Harris NR
Harris NR
中科院分区:
医学3区
文献类型:
--
作者:
Lee M;Leskova W;Eshaq RS;Harris NR

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据报道,甲基苯丙胺(METH)滥用者中存在视网膜中央动脉阻塞、视网膜病变和视网膜新生血管。在目前的研究中,我们研究了METH是否在小鼠模型中诱导视网膜新生血管形成,如果是这样,新生血管形成是否与缺氧、缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)的增加有关。在26天的时间内通过腹膜内注射向小鼠施用METH,或注射盐水作为载体对照。在用异硫氰酸荧光素-葡聚糖输注后,使用体内实时成像对视网膜小动脉和小静脉的数量进行计数。用griffonia simplicifolia凝集素I对切除的视网膜进行染色,并用AngioTool将其平放以测量血管分布(每个组织面积的血管长度)。通过抗哌莫硝唑抗体与哌莫硝唑形成加合物(Hypoxyprobe)检测视网膜缺氧,免疫印迹法检测视网膜中HIF-1α和VEGFa蛋白水平。METH给药增加了第26天测量的血管分布(包括小动脉数量)。在第5天,METH处理的小鼠中视网膜VEGFa蛋白水平没有变化,但在第12天和第26天增加。在第12天和第26天,MET处理的小鼠视网膜中缺氧(哌莫硝唑加合物形成)增加,HIF-1α蛋白表达水平也增加。这些结果表明,METH给药诱导视网膜中的缺氧、HIF-1α、VEGFa和血管生成。
Central retinal artery occlusion, retinopathy, and retinal neovascularization have been reported in methamphetamine (METH) abusers. In the current study, we investigated whether METH induces retinal neovascularization in a mouse model, and if so, whether the neovascularization is associated with increased hypoxia, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF). Mice were administrated METH by intraperitoneal injection over a 26-day period, or injected with saline as a vehicle control. The number of retinal arterioles and venules were counted using in vivo live imaging following infusion with fluorescein isothiocyanate-dextran. Excised retinas were stained with griffonia simplicifolia lectin I and flat mounted for a measurement of vascularity (length of vessels per tissue area) with AngioTool. Retinal hypoxia was examined by formation of pimonidazole (Hypoxyprobe) adducts with anti-pimonidazole antibody, and HIF-1α and VEGFa protein levels in the retina were detected by immunoblot. METH administration increased vascularity (including the number of arterioles) measured on Day 26. Retinal VEGFa protein level was not changed in METH-treated mice on Day 5, but was increased on Day 12 and Day 26. Hypoxia (pimonidazole adduct formation) was increased in retinas of METH-treated mice on Day 12 and Day 26, as were HIF-1α protein expression levels. These results indicate that METH administration induces hypoxia, HIF-1α, VEGFa, and angiogenesis in the retina.
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