Background: 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.
Methods: 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.
Conclusion: 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.