Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Cancer Research Center, Boston University School of Medicine, Boston, MA, USA.
Biochem Pharmacol. 2022 Sep;203:115168. doi: 10.1016/j.bcp.2022.115168. Epub 2022 Jul 12.
Pathological deterioration of mitochondrial function is increasingly linked with multiple degenerative illnesses as a mediator of a wide range of neurologic and age-related chronic diseases, including those of genetic origin. Several of these diseases are rare, typically defined in the United States as an illness affecting fewer than 200,000 people in the U.S. population, or about one in 1600 individuals. Vision impairment due to mitochondrial dysfunction in the eye is a prominent feature evident in numerous primary mitochondrial diseases and is common to the pathophysiology of many of the familiar ophthalmic disorders, including age-related macular degeneration, diabetic retinopathy, glaucoma and retinopathy of prematurity - a collection of syndromes, diseases and disorders with significant unmet medical needs. Focusing on metabolic mitochondrial pathway mechanisms, including the possible roles of cuproptosis and ferroptosis in retinal mitochondrial dysfunction, we shed light on the potential of α-lipoyl-L-carnitine in treating eye diseases. α-Lipoyl-L-carnitine is a bioavailable mitochondria-targeting lipoic acid prodrug that has shown potential in protecting against retinal degeneration and photoreceptor cell loss in ophthalmic indications.
线粒体功能的病理性恶化与多种退行性疾病越来越相关，作为多种神经和与年龄相关的慢性疾病的中介，包括那些具有遗传起源的疾病。这些疾病中有几种是罕见的，通常在美国被定义为影响美国人口中少于 20 万人的疾病，即每 1600 个人中就有一个。由于眼睛中线粒体功能的障碍导致的视力损害是许多原发性线粒体疾病的一个显著特征，也是许多常见眼科疾病的病理生理学的共同特征，包括年龄相关性黄斑变性、糖尿病性视网膜病变、青光眼和早产儿视网膜病变——这些疾病包括了许多综合征、疾病和病症，它们都存在着显著的未满足的医疗需求。我们专注于代谢性线粒体途径机制，包括铜死亡和铁死亡在视网膜线粒体功能障碍中的可能作用，揭示了 α-硫辛酸-L-肉碱在治疗眼部疾病方面的潜力。α-硫辛酸-L-肉碱是一种生物可利用的线粒体靶向硫辛酸前体药物，已显示出在眼科适应症中预防视网膜变性和光感受器细胞损失方面的潜力。
