Therapeutic targets for altering mitochondrial dysfunction associated with diabetic retinopathy.
Therapeutic targets for altering mitochondrial dysfunction associated with diabetic retinopathy.
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DOI：
10.1080/14728222.2018.1439921
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发表时间：
2018-03
影响因子：
5.8
通讯作者：
Mishra M
中科院分区：
文献类型：
--
作者：
Kowluru RA;Mishra M
视网膜病变仍然是糖尿病最可怕的致盲并发症之一，随着这种终身疾病的患病率以惊人的速度上升，视网膜病变的发病率也在攀升。尽管前沿研究已经确定了许多与其发展相关的分子机制，但糖尿病如何损害视网膜的确切机制仍然不清楚，限制了这种毁灭性疾病的治疗选择。本文综述了线粒体功能障碍/损伤在糖尿病视网膜病变发病机制中的核心作用，以及受损的线粒体如何启动自由基的自我维持恶性循环。我们还回顾了线粒体如何作为治疗靶点，以及与复杂的双线粒体膜和明确的血液-视网膜屏障相关的挑战，以获得改善线粒体功能的最佳药理学/分子方法。线粒体功能障碍为改善糖尿病视网膜病变的发展提供了许多治疗靶点，包括其生物起源、DNA损伤和表观遗传修饰。增强线粒体内药物摄取的新技术，将药物递送到视网膜的纳米技术，以及通过改变生活方式和防止表观遗传修饰的新疗法来维持线粒体稳态，可以作为糖尿病患者靶向这种视力威胁疾病的一些欢迎途径。
Retinopathy remains as one of the most feared blinding complications of diabetes, and with the prevalence of this life-long disease escalating at an alarming rate, the incidence of retinopathy is also climbing. Although the cutting edge research has identified many molecular mechanisms associated with its development, the exact mechanism how diabetes damages the retina remains obscure, limiting therapeutic options for this devastating disease. This review focuses on the central role of mitochondrial dysfunction/damage in the pathogenesis of diabetic retinopathy, and how damaged mitochondria initiates a self-perpetuating vicious cycles of free radicals. We have also reviewed how mitochondria could serve as a therapeutic target, and the challenges associated with the complex double mitochondrial membranes and a well-defined blood-retinal barrier for optimal pharmacologic/molecular approach to improve mitochondrial function. Mitochondrial dysfunction provides many therapeutic targets for ameliorating the development of diabetic retinopathy including their biogenesis, DNA damage and epigenetic modifications. New technology to enhance pharmaceuticals uptake inside the mitochondria, nanotechnology to deliver drugs to the retina, and maintenance of mitochondrial homeostasis via lifestyle changes and novel therapeutics to prevent epigenetic modifications, could serve as some of the welcoming avenues for a diabetic patient to target this sight-threatening disease.
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