PDF(Pubmed)
Abstract：
Diabetic retinopathy (DR) is a leading cause of blindness and vision impairment worldwide and represents one of the most common complications among diabetic patients. Current treatment modalities for DR, including laser photocoagulation, intravitreal injection of corticosteroid, and anti-vascular endothelial growth factor (VEGF) agents, target primarily vascular lesions. However, these approaches are invasive and have several limitations, such as potential loss of visual function, retinal scars and cataract formation, and increased risk of ocular hypertension, vitreous hemorrhage, retinal detachment, and intraocular inflammation. Recent studies have suggested mitochondrial dysfunction as a pivotal factor leading to both the vascular and neural damage in DR. Given that Coenzyme Q10 (CoQ10) is a proven mitochondrial stabilizer with antioxidative properties, this study investigated the effect of CoQ10 eyedrops [in conjunction with vitamin E d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)] on DR-induced neurodegeneration using a type 2 diabetes mouse model (C57BLKsJ-db/db mice). Utilizing a comprehensive electroretinography protocol, supported by immunohistochemistry, our results revealed that topical application of CoQ10 eyedrops conjugated with vitamin E TPGS produced a neuroprotective effect against diabetic-induced neurodegeneration by preserving the function and histology of various retinal neural cell types. Compared to the control group, mice treated with CoQ10 exhibited thicker outer and inner nuclear layers, higher densities of photoreceptor, cone cell, and rod-bipolar cell dendritic boutons, and reduced glial reactivity and microglial cell density. Additionally, the CoQ10 treatment significantly alleviated retinal levels of MMP-9 and enhanced mitochondrial function. These findings provide further insight into the role of mitochondrial dysfunction in the development of DR and suggest CoQ10 eyedrops, conjugated with vitamin E TPGS, as a potential complementary therapy for DR-related neuropathy.
摘要：
糖尿病视网膜病变（DR）是全球范围内失明和视力障碍的主要原因，并且是糖尿病患者中最常见的并发症之一。目前DR的治疗方式，包括激光光凝，玻璃体内注射皮质类固醇，和抗血管内皮生长因子（VEGF）药物，目标主要是血管病变。然而,这些方法是侵入性的，有几个局限性，例如潜在的视觉功能丧失，视网膜疤痕和白内障的形成，和高眼压的风险增加，玻璃体出血,视网膜脱离,和眼内炎症。最近的研究表明，线粒体功能障碍是导致DR血管和神经损伤的关键因素。鉴于辅酶Q10（CoQ10）是一种公认的具有抗氧化特性的线粒体稳定剂，这项研究使用2型糖尿病小鼠模型（C57BLKsJ-db/db小鼠）研究了CoQ10滴眼液[与维生素Ed-α-生育酚聚（乙二醇）1000琥珀酸酯（TPGS）联用]对DR诱导的神经变性的影响。利用全面的视网膜电图协议，由免疫组织化学支持，我们的结果显示,局部应用CoQ10滴眼液与维生素ETPGS结合,通过保留各种视网膜神经细胞类型的功能和组织学,对糖尿病诱导的神经变性产生了神经保护作用.与对照组相比,用CoQ10治疗的小鼠表现出较厚的外核和内核层，更高密度的感光体，视锥细胞,和杆状双极细胞树突状突起，并降低神经胶质反应性和小胶质细胞密度。此外,CoQ10治疗可显着减轻视网膜MMP-9的水平并增强线粒体功能。这些发现为线粒体功能障碍在DR发展中的作用提供了进一步的见解，并建议使用CoQ10滴眼液，与维生素ETPGS结合，作为DR相关神经病的潜在补充疗法。
