Metalloproteinase Adamts16 Is Required for Proper Closure of the Optic Fissure
Metalloproteinase Adamts16 Is Required for Proper Closure of the Optic Fissure
复制标题
正确闭合视裂需要金属蛋白酶 Adamts16
DOI：
10.1167/iovs.17-22827
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发表时间：
2018-03-01
影响因子：
4.4
通讯作者：
Chen, Shuyi
中科院分区：
文献类型：
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作者：
Cao, Mingzhe;Ouyang, Jiamin;Chen, Shuyi
目的。视网膜缺损是一种因视神经裂隙（OF）闭合失败而引起的威胁视力的先天性眼病。本研究的目的是探讨金属蛋白酶Adamts16在of关闭中的作用。采用RNA原位杂交技术检测Adamts16在发育中的小鼠和斑马鱼眼中的表达。在斑马鱼眼睛发育过程中，进行了Morpholino敲低以研究adamts16的功能。此外，通过免疫荧光染色、RNA原位杂交、溴脱氧尿苷（BrdU）标记、TUNEL检测和高通量测序，研究了adamts16-morphant optic cups （OCs）中细胞和分子事件的变化。Adamts16在小鼠和斑马鱼眼睛闭合边缘表达。斑马鱼adamts16敲低导致结肠形成。在adamts16型眼中，基底膜在边缘闭合处无法解体，OC细胞增殖减少，凋亡增加，成纤维细胞生长因子8 （fgf8）在OC中异位上调。在斑马鱼的眼睛中，需要adamts16来进行适当的封闭。adamts16可能通过降解边缘闭合处的基底膜、促进细胞增殖和存活以及限制fgf8的表达来控制OF闭合。我们的研究将金属蛋白酶与OF闭合联系起来，这可能有助于未来对人类结肠瘤病例的病因学研究。
PURPOSE. Coloboma is a sight-threatening congenital eye disease caused by a failure in optic fissure (OF) closure. The aim of this study was to investigate the role of Adamts16, a metalloproteinase, in OF closure.METHODS. RNA in situ hybridization was used to examine the expression of Adamts16 in developing mouse and zebrafish eyes. Morpholino knockdowns were performed to study adamts16 function during zebrafish eye development. Additionally, immunofluorescent staining, RNA in situ hybridization, bromodeoxyuridine (BrdU) labeling, TUNEL assays, and high-throughput sequencing were used to examine altered cellular and molecular events in adamts16-morphant optic cups (OCs).RESULTS. Adamts16 is expressed at the edges of the closing OF in both mice and zebrafish eyes. Zebrafish adamts16 knockdown resulted in coloboma formation. In adamts16-morphant eyes, the basement membrane failed to disassemble at the closing OF edges, OC cells exhibited decreased proliferation and increased apoptosis, and fibroblast growth factor 8 (fgf8) was ectopically upregulated in the OC.CONCLUSIONS. adamts16 is required for proper OF closure in zebrafish eyes. adamts16 controls OF closure possibly through the combined functions of degrading the basement membrane at the closing OF edges, promoting cell proliferation and survival, and restricting fgf8 expression. Our study linked a metalloproteinase to OF closure, which may facilitate future etiologic studies on human coloboma cases.