Endothelial Activation and Oxidative Stress in Neurovascular Defects of the Retina

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.