Targeting the HDAC6-Cilium Axis Ameliorates the Pathological Changes Associated with Retinopathy of Prematurity.
Targeting the HDAC6-Cilium Axis Ameliorates the Pathological Changes Associated with Retinopathy of Prematurity.
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靶向 HDAC6-纤毛轴可改善与早产儿视网膜病变相关的病理变化
DOI：
10.1002/advs.202105365
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发表时间：
2022-07
期刊：
影响因子：
15.1
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
--
作者：
Ran, Jie;Zhang, Yao;Zhang, Sai;Li, Haixia;Zhang, Liang;Li, Qingchao;Qin, Juan;Li, Dengwen;Sun, Lei;Xie, Songbo;Zhang, Xiaomin;Liu, Lin;Liu, Min;Zhou, Jun
早产儿视网膜病变（ROP）是儿童视力障碍和失明的主要原因之一。然而，对于ROP的有效药物干预仍然很少。组蛋白去乙酰化酶6（HDAC 6）介导的光感受器纤毛解体最近被认为是ROP发病机制中的早期事件。本文显示，通过玻璃体内注射编码HDAC 6的腺病毒来增强HDAC 6的表达诱导了小鼠中与ROP相关的典型病理变化，包括光感受器外节的膜盘的破坏和视网膜电图振幅的降低。Hdac 6转基因小鼠在视网膜结构和功能以及光感受器纤毛的分解方面表现出类似的ROP相关缺陷，而Hdac 6敲除小鼠对氧变化诱导的视网膜缺陷具有抗性。进一步显示，通过玻璃体内注射小分子化合物来阻断HDAC 6介导的纤毛解体保护小鼠免受ROP相关的视网膜缺陷。研究结果表明，HDAC 6-纤毛轴的药理学靶向可能是预防ROP的一种有前途的策略。在本文中，作者表明，小鼠中组蛋白脱乙酰酶6（HDAC 6）的过表达诱导与早产儿视网膜病变（ROP）相关的典型病理变化，ROP是一种影响早产儿的眼病。阻断HDAC 6介导的感光细胞纤毛解体可保护小鼠免受ROP相关的视网膜缺陷。这项工作支持了这样一种观点，即靶向HDAC 6-纤毛轴有望预防ROP。
Retinopathy of prematurity (ROP) is one of the leading causes of childhood visual impairment and blindness. However, there are still very few effective pharmacological interventions for ROP. Histone deacetylase 6 (HDAC6)‐mediated disassembly of photoreceptor cilia has recently been implicated as an early event in the pathogenesis of ROP. Herein it is shown that enhanced expression of HDAC6 by intravitreal injection of adenoviruses encoding HDAC6 induces the typical pathological changes associated with ROP in mice, including disruption of the membranous disks of photoreceptor outer segments and a decrease in electroretinographic amplitudes. Hdac6 transgenic mice exhibit similar ROP‐related defects in retinal structures and functions and disassembly of photoreceptor cilia, whereas Hdac6 knockout mice are resistant to oxygen change‐induced retinal defects. It is further shown that blocking HDAC6‐mediated cilium disassembly by intravitreal injection of small‐molecule compounds protect mice from ROP‐associated retinal defects. The findings indicate that pharmacological targeting of the HDAC6‐cilium axis may represent a promising strategy for the prevention of ROP. Herein the authors show that overexpression of histone deacetylase 6 (HDAC6) in mice induces the typical pathological changes associated with retinopathy of prematurity (ROP), an eye disease affecting premature infants. Blocking HDAC6‐mediated photoreceptor cilium disassembly protects mice from ROP‐associated retinal defects. This work supports the notion that targeting the HDAC6‐cilium axis holds promise for the prevention of ROP.
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影响因子：
7.2
作者：
Bujakowska KM;Liu Q;Pierce EA
通讯作者：
Pierce EA
影响因子：
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