Genetic determinants of hyaloid and retinal vasculature in zebrafish.

Genetic determinants of hyaloid and retinal vasculature in zebrafish.
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DOI:
10.1186/1471-213x-7-114
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发表时间:
2007-10-15
影响因子:
--
通讯作者:
Kennedy BN
Kennedy BN
中科院分区:
生物学4区
文献类型:
--
作者:
Alvarez Y;Cederlund ML;Cottell DC;Bill BR;Ekker SC;Torres-Vazquez J;Weinstein BM;Hyde DR;Vihtelic TS;Kennedy BN

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视网膜脉管系统是覆盖大多数哺乳动物的内部视网膜的血管的毛细血管网络。视网膜血管系统中的发育异常或微血管并发症导致导致失明的严重人类眼部疾病。为了利用斑马鱼的优势进行视网膜血管的遗传、发育和药理学研究,我们对斑马鱼眼内血管进行了表征。我们展示了斑马鱼视网膜血液供应的详细形态学和发育分析。与哺乳动物胚胎中的短暂玻璃体脉管系统相似,在受精后2.5天首次发现血管附着在斑马鱼透镜上。这些血管逐渐失去与透镜的接触,并在受精后30天粘附到幼年视网膜的内界膜上。超微结构分析显示这些血管具有哺乳动物视网膜血管系统的独特特征。例如,平滑肌肌动蛋白表达的周细胞被血管的基底层包裹,并且存在囊泡空泡细胞器(VVO),血管-视网膜营养的亚细胞介质。最后,我们确定了9个基因与细胞膜,细胞外基质和未知身份是必要的斑马鱼玻璃体和视网膜血管发育。斑马鱼具有视网膜血液供应,具有特征性的发育和成年形态。很容易观察到这些眼内血管的脱落,从而能够在斑马鱼中应用遗传和化学方法来识别发育和疾病中玻璃体和视网膜血管系统的分子调节因子。
The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish. We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO), subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development. Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.