Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN. 38163, United States.
Department of Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, TN, 38163, United States.
Curr Pharm Des. 2018;24(40):4742-4754. doi: 10.2174/1381612825666190115122622.
The eye is considered as a window of the disease, and a better understanding of neurodegenerative changes in the eye may help diagnose and manage neurodegenerative diseases including the diseases of brain, heart, kidney and liver. In the eye, the blood retinal barrier (BRB] is maintained by a combination of endothelial cells, pericytes, and glia. This BRB integrity is fundamental to the physiology of retinal cellular function and accurate vision. The role of endothelial dysfunction as a consequence of endothelial activation in the initiation and prolongation of neurovascular diseases of the retina is emerging.
The observations made in this article are a result of our research over the years in the subject matter and also based on a literature search using PubMed with keywords including but not limited to endothelial, permeability, oxidative stress, ROS, TNF-α, retina, injury, and neurodegeneration. Several studies were identified that fulfilled the inclusion criteria. Overall, published studies support an association between endothelial activation, inflammation and oxidative stress in retinal diseases. Although the selection of specific endothelial activation biomarkers in the retina is less clear, there is an increased association between inflammation in the severity of diabetic retinopathy. Studies in other clinically relevant studies demonstrated a strong association of endothelial activation to alterations in mitochondrial respiratory chain complexes, pericyte integrity, microglial activation, neutrophil extracellular traps and elevated plasma concentrations of TNF-α.
The compromise in BRB as a consequence of the neurovascular unit in the retinal tissue has gained a lot of attention and studies addressing these should result in a better understanding of the pathophysiology of retinal diseases. Although there are no specific retinal markers of endothelial activation and inflammation, future studies using specific models that display endothelial activation, inflammation and oxidative stress likely yield better understanding on the cause or effect relationship of endothelial activation in retinal diseases.
眼睛被认为是疾病的窗口，更好地了解眼部神经退行性变化可能有助于诊断和治疗包括脑部、心脏、肾脏和肝脏疾病在内的神经退行性疾病。在眼睛中，血视网膜屏障（BRB）由内皮细胞、周细胞和神经胶质细胞共同维持。这种 BRB 完整性对于视网膜细胞功能和准确视力的生理学至关重要。内皮功能障碍作为视网膜神经血管疾病发生和持续的内皮激活的结果的作用正在显现。
本文中的观察结果是我们多年来在该主题上的研究结果，也是基于使用 PubMed 进行的文献搜索得出的，关键词包括但不限于内皮、通透性、氧化应激、ROS、TNF-α、视网膜、损伤和神经退行性变。确定了几项符合纳入标准的研究。总的来说，已发表的研究支持内皮激活、炎症和氧化应激与视网膜疾病之间的关联。尽管在视网膜中选择特定的内皮激活生物标志物不太明确，但炎症与糖尿病视网膜病变的严重程度之间的关联增加。其他临床相关研究中的研究表明，内皮激活与线粒体呼吸链复合物、周细胞完整性、小胶质细胞激活、中性粒细胞细胞外陷阱和 TNF-α 血浆浓度升高的改变之间存在很强的关联。
由于视网膜组织中的神经血管单元，BRB 的受损引起了广泛关注，针对这些问题的研究应该有助于更好地了解视网膜疾病的病理生理学。尽管没有特定的内皮激活和炎症的视网膜标志物，但使用显示内皮激活、炎症和氧化应激的特定模型进行的未来研究可能会更好地理解内皮激活在视网膜疾病中的因果关系。
