a Department of Ophthalmology, Kresge Eye Institute , Wayne State University , Detroit , MI , USA.
Expert Opin Ther Targets. 2018 Mar;22(3):233-245. doi: 10.1080/14728222.2018.1439921.
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. Areas covered: 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. Expert opinion: 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.
糖尿病性视网膜病变仍然是最令人恐惧的致盲并发症之一，随着这种终身疾病的发病率以惊人的速度上升，视网膜病变的发病率也在攀升。虽然前沿研究已经确定了许多与糖尿病性视网膜病变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不清楚，这限制了治疗这种破坏性疾病的选择。
本篇综述重点介绍了线粒体功能障碍/损伤在糖尿病性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引发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，以及复杂的双层线粒体膜和明确的血视网膜屏障对优化药理学/分子方法以改善线粒体功能所带来的挑战。
线粒体功能障碍为改善糖尿病性视网膜病变的发展提供了许多治疗靶点，包括其生物发生、DNA 损伤和表观遗传修饰。增强药物在线粒体内部摄取的新技术、将药物递送到视网膜的纳米技术以及通过生活方式改变和新型治疗药物维持线粒体动态平衡以预防表观遗传修饰，这些都可以成为糖尿病患者针对这种致盲性疾病的一些有前景的方法。
