The stress response protein REDD1 as a causal factor for oxidative stress in diabetic retinopathy.
The stress response protein REDD1 as a causal factor for oxidative stress in diabetic retinopathy.
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应力反应蛋白REDD1是糖尿病性视网膜病中氧化应激的因素。
DOI：
10.1016/j.freeradbiomed.2021.01.041
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发表时间：
2021-03
影响因子：
7.4
通讯作者：
Dennis MD
中科院分区：
文献类型：
--
作者：
Miller WP;Sunilkumar S;Dennis MD
糖尿病视网膜病变（DR）是导致视觉功能障碍的主要原因，但有关糖尿病诱导的视网膜病理生理学的特定分子事件仍知之甚少。在此，我们回顾了氧化应激对DR的影响，并探讨了支持应激反应蛋白在糖尿病诱导的氧化应激和视力功能缺陷的发展中的关键作用的证据。已经确定，REDD 1通过抑制称为雷帕霉素复合物1（mTORC 1）的机制靶点的中央代谢调节因子，介导细胞对多种不同应激源的反应。越来越多的证据也支持REDD 1独立于mTORC 1通过增强活性氧的产生和抑制抗氧化反应来促进氧化应激。总的来说，有强有力的临床前数据支持REDD 1在糖尿病引起的视网膜并发症的发展和进展中的关键作用。此外，早期的概念验证临床试验已经发现，通过玻璃体内递送靶向REDD1 mRNA的siRNA，在对抗缺血性视网膜疾病方面取得了一定程度的成功。总的来说，REDD1相关的信号转导代表了一个有趣的新的临床治疗目标，通过靶向导致DR的潜在分子机制来解决糖尿病症状。
Diabetic Retinopathy (DR) is a major cause of visual dysfunction, yet much remains unknown regarding the specific molecular events that contribute to diabetes-induced retinal pathophysiology. Herein, we review the impact of oxidative stress on DR, and explore evidence that supports a key role for the stress response protein regulated in development and DNA damage (REDD1) in the development of diabetes-induced oxidative stress and function defects in vision. It is well established that REDD1 mediates the cellular response to a number of diverse stressors through repression of the central metabolic regulator known as mechanistic target of rapamycin complex 1 (mTORC1). A growing body of evidence also supports that REDD1 acts independent of mTORC1 to promote oxidative stress by both enhancing the production of reactive oxygen species and suppressing the antioxidant response. Collectively, there is strong preclinical data to support a key role for REDD1 in the development and progression of retinal complications caused by diabetes. Furthermore, early proof-of-concept clinical trials have found a degree of success in combating ischemic retinal disease through intravitreal delivery of an siRNA targeting the REDD1 mRNA. Overall, REDD1-associated signaling represents an intriguing target for novel clinical therapies that go beyond addressing the symptoms of diabetes by targeting the underlying molecular mechanisms that contribute to DR.
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影响因子：
4.4
作者：
Deliyanti, Devy;Alrashdi, Saeed F.;Wilkinson-Berka, Jennifer L.
通讯作者：
Wilkinson-Berka, Jennifer L.
影响因子：
--
作者：
Afanas'ev I
通讯作者：
Afanas'ev I
影响因子：
15.9
作者：
Barber, AJ;Lieth, E;Gardner, TW
通讯作者：
Gardner, TW
DOI：
10.1016/s09254439(02)00219-3
发表时间：
2003-01-20
影响因子：
6.2
作者：
Beisswenger, PJ;Howell, SK;Szwergold, BS
通讯作者：
Szwergold, BS
影响因子：
5.4
作者：
Britto FA;Cortade F;Belloum Y;Blaquière M;Gallot YS;Docquier A;Pagano AF;Jublanc E;Bendridi N;Koechlin-Ramonatxo C;Chabi B;Francaux M;Casas F;Freyssenet D;Rieusset J;Giorgetti-Peraldi S;Carnac G;Ollendorff V;Favier FB
通讯作者：
Favier FB