Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.
Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.
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DOI：
10.1007/978-3-319-17121-0_6
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发表时间：
2016
影响因子：
--
通讯作者：
Kleinman ME
中科院分区：
文献类型：
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作者：
Berner AK;Kleinman ME
最近的数据显示，表观遗传紊乱和随后的染色质重塑是慢性炎症和细胞存活的有效生物开关，这是几种视网膜变性发病机制中的重要治疗靶点。组蛋白脱乙酰酶（HDAC）是该系统的主要组成部分，并作为染色质重塑过程的独特控制。随着现在有许多靶向HDAC抑制剂，它们在基础科学和临床研究中的应用已经大大扩大。在眼部生物学领域，有数据表明HDAC抑制可以抑制新血管形成，并且可能是视网膜色素变性和干性年龄相关性黄斑变性（AMD）的可能治疗。然而，这些抑制剂对脉络膜视网膜组织中细胞存活和趋化因子表达的影响仍然非常不清楚。在这里，我们回顾了HDAC活性和药理学抑制的多方面生物学，同时进一步深入了解这种表观遗传途径在视网膜变性中的重要性。我们的实验室研究旨在开辟翻译途径，以推进干性AMD治疗，同时探索乙酰化对炎症基因表达在老化和变性视网膜中的作用。
Recent data have revealed epigenetic derangements and subsequent chromatin remodeling as a potent biologic switch for chronic inflammation and cell survival which are important therapeutic targets in the pathogenesis of several retinal degenerations. Histone deacetylases (HDACs) are a major component of this system and serve as a unique control of the chromatin remodeling process. With a multitude of targeted HDAC inhibitors now available, their use in both basic science and clinical studies has widened substantially. In the field of ocular biology, there are data to suggest that HDAC inhibition may suppress neovascularization and may be a possible treatment for retinitis pigmentosa and dry age-related macular degeneration (AMD). However, the effects of these inhibitors on cell survival and chemokine expression in the chorioretinal tissues remain very unclear. Here, we review the multifaceted biology of HDAC activity and pharmacologic inhibition while offering further insight into the importance of this epigenetic pathway in retinal degenerations. Our laboratory investigations aim to open translational avenues to advance dry AMD therapeutics while exploring the role of acetylation on inflammatory gene expression in the aging and degenerating retina.