Epigenetics and Signaling Pathways in Glaucoma.
Epigenetics and Signaling Pathways in Glaucoma.
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DOI：
10.1155/2017/5712341
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发表时间：
2017
影响因子：
--
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Gauthier AC;Liu J
青光眼是全世界最常见的不可逆失明原因。随着年龄的增长，这种神经退行性疾病变得更加普遍，但易感的遗传和环境因素也会增加风险。现在新出现的证据表明，表观遗传学也可能参与其中，这提供了潜在的新治疗靶点。这三种因子通过多种途径发挥作用，包括TGF-β、MAP激酶、Rho激酶、BDNF、JNK、PI-3/Akt、PTEN、Bcl-2、Caspase和钙- calpain信号。总之，这些途径导致促凋亡基因表达上调，神经保护因子和促存活因子下调，以及小梁网纤维化的产生，这可能会阻断房水引流。针对这些通路成员的新型治疗剂已经在动物模型甚至人体试验中显示出初步的成功，表明它们最终可能用于保护视网膜神经元和视力。
Glaucoma is the most common cause of irreversible blindness worldwide. This neurodegenerative disease becomes more prevalent with aging, but predisposing genetic and environmental factors also contribute to increased risk. Emerging evidence now suggests that epigenetics may also be involved, which provides potential new therapeutic targets. These three factors work through several pathways, including TGF-β, MAP kinase, Rho kinase, BDNF, JNK, PI-3/Akt, PTEN, Bcl-2, Caspase, and Calcium-Calpain signaling. Together, these pathways result in the upregulation of proapoptotic gene expression, the downregulation of neuroprotective and prosurvival factors, and the generation of fibrosis at the trabecular meshwork, which may block aqueous humor drainage. Novel therapeutic agents targeting these pathway members have shown preliminary success in animal models and even human trials, demonstrating that they may eventually be used to preserve retinal neurons and vision.