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Longitudinal visualization of vascular occlusion, reperfusion, and remodeling in a zebrafish model of retinal vascular leakage using OCT angiography

机译:使用OCT血管造影术在斑马鱼视网膜血管渗漏模型中对血管闭塞,再灌注和重塑进行纵向可视化

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Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two of the leading causes of blindness and visual impairment in the world. Neovascularization results in severe vision loss in DR and AMD and, thus, there is an unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a leading model organism for studying human disease pathogenesis, and the highly conserved drug activity between zebrafish and humans and their ability to readily absorb small molecules dissolved in water has benefited pharmaceutical discovery. Here, we use optical coherence tomography (OCT) and OCT angiography (OCT-A) to perform noninvasive, in vivo retinal imaging in a zebrafish model of vascular leakage. Zebrafish were treated with diethylaminobenzaldehyde (DEAB) to induce vascular leakage and imaged with OCT and OCT-A at six time points over two weeks: baseline one day before treatment and one, three, six, eight, and ten days post treatment. Longitudinal functional imaging showed significant vascular response immediately after DEAB treatment. Observed vascular changes included partial or complete vascular occlusion immediately after treatment and reperfusion during a two-week period. Increased vascular tortuosity several days post treatment indicated remodeling, and bifurcations and collateral vessel formation were also observed. In addition, significant treatment response variabilities were observed in the contralateral eye of the same animal. Anatomical and functional normalization was observed in most animals by ten days post treatment. These preliminary results motivate potential applications of OCT-A as a tool for studying pathogenesis and therapeutic screening in zebrafish models of retinal vascular disease.
机译:糖尿病性视网膜病(DR)和年龄相关性黄斑变性(AMD)是世界上失明和视力障碍的两个主要原因。新血管形成导致DR和AMD的严重视力丧失,因此,尚未找到确定发病机理和新型抗血管生成疗法的需求。斑马鱼是研究人类疾病发病机理的主要模型生物,斑马鱼与人类之间高度保守的药物活性及其易于吸收溶解在水中的小分子的能力已为药物开发带来了好处。在这里,我们使用光学相干断层扫描(OCT)和OCT血管造影(OCT-A)在斑马鱼血管渗漏模型中执行无创性体内视网膜成像。用二乙氨基苯甲醛(DEAB)处理斑马鱼以诱导血管渗漏,并在两周的六个时间点使用OCT和OCT-A进行成像:治疗前一天的基线和治疗后一,三,六,八和十天的基线。纵向功能成像显示DEAB治疗后立即有明显的血管反应。治疗后两周内观察到的血管变化包括部分或完全的血管闭塞,并立即进行了再灌注。治疗后几天血管曲折度增加表明重塑,并且也观察到分叉和侧支血管形成。此外,在同一只动物的对侧眼中观察到显着的治疗反应差异。在治疗后十天,在大多数动物中观察到解剖学和功能正常化。这些初步结果激发了OCT-A作为研究视网膜血管疾病斑马鱼模型的发病机理和治疗筛选的工具的潜在应用。

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