Repressed Wnt Signaling Accelerates the Aging Process in Mouse Eyes.
Repressed Wnt Signaling Accelerates the Aging Process in Mouse Eyes.
复制标题
抑制 Wnt 信号会加速小鼠眼睛的衰老过程。
DOI：
10.1155/2019/7604396
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发表时间：
2019
影响因子：
1.9
通讯作者：
Yuan,Yong
中科院分区：
文献类型：
--
作者：
Zhang,Yujin;Jeffrey,Joseph;Dong,Fei;Zhang,Jianhua;Kao,WinstonW-Y;Liu,Chia-Yang;Yuan,Yong
目的。眼睛老化是视力功能衰退的自然过程。当这一过程达到影响正常日常活动的程度时，就会表现为与年龄相关的眼部疾病，如年龄相关性黄斑变性、白内障、青光眼和假性剥脱综合征。我们以前曾报道，在组织发育过程中，抑制的Wnt信号加速了角膜上皮的成熟。在这里，我们探索了Wnt信号被抑制与小鼠眼睛加速衰老有关的假设。WNT配体拮抗剂分泌的卷曲相关蛋白1(SFRP1)通过组织特异性、诱导性、双反式系统在角膜基质中表达。对组织结构进行分析，以寻找衰老的迹象。信号转导分析确定细胞对sFRP1的反应。表达SFRP1的小鼠眼睛显示出加速衰老的迹象，类似于假性剥脱(PEX)综合征，这是一种已知的与年龄相关的疾病。具体表现包括晶状体前囊膜表面颗粒状沉积，虹膜前表面色素丢失，前房内纤维物质的存在，角膜内皮细胞大小和形态的改变(多形性)。体外研究表明，SFRP1不抑制WNT5a的功能，细胞对SFRP1和WNT5a的反应方式非常相似。SFRP1的表达加速了小鼠眼睛的衰老过程，未来的研究将有必要阐明其潜在的机制。
Purpose. Ocular aging is a natural process of functional decline in vision. When the process reaches a point that compromised vision affects normal daily activity, it manifests as age‐related ocular diseases, such as age‐related macular degeneration, cataracts, glaucoma, and pseudoexfoliation syndrome. We previously reported that repressed Wnt signaling accelerated the maturation of corneal epithelium during tissue development. Here, we explore the hypothesis that repressed Wnt signaling is associated with accelerated aging in mouse eyes.Methods. Wnt ligand antagonist secreted frizzled‐related protein 1 (sFRP1) was expressed in the corneal stroma by a tissue‐specific, inducible, bitransgenic system. Tissue structure was analyzed for signs of aging. Signal transduction analysis was performed to determine the cellular response to sFRP1.Results. Mouse eyes with sFRP1 expression showed signs of accelerated aging, resembling those found in pseudoexfoliation (PEX) syndrome, a known age‐related disease. Specific findings include granular deposition on the surface of the anterior lens capsule, pigment loss from the anterior surface of the iris, the presence of fibrillary material in the anterior chamber, and changes in cell size (polymegethism) and shape (pleomorphism) of the corneal endothelial cells.In vitrostudies demonstrated that sFRP1 did not inhibit Wnt5a function and that cells responded to sFRP1 and Wnt5a in a very similar manner.Conclusion. The expression of sFRP1 accelerates the aging process in mouse eyes and future studies are warranted to elucidate the underlying mechanisms.