Tie2 Pathway - A Key Regulator of Vascular Stability
The Tie2 pathway was discovered 20 years ago. Since that time considerable scientific evidence has established active Tie2 as a key regulator of vascular stability.
Tie2 is activated by the binding of the ligand, angiopoietin-1 (Ang-1). In the retina, Ang-1 is predominantly produced by pericytes that surround retinal capillaries. Activated Tie2 is responsible for the maintenance of vascular stability and quiescence in normal, healthy vasculature.
Tie2 activity is downregulated by two mechanisms: deactivation of active Tie2 by vascular endothelial protein tyrosine phosphatase (VE-PTP) and binding of the non-activating ligand angiopoietin-2 (Ang-2).
Both VE-PTP and Ang-2 are upregulated by hypoxia and tissue ischemia, conditions that are associated with vasculopathy and are characterized by endothelial dysfunction, and vascular destabilization. These conditions include retinopathies such diabetic eye disease, wet age-related macular degeneration, retinal vein occlusion and non-ocular diabetic comorbidities such as nephropathy.
VE-PTP deactivates active Tie2 on the intracellular side of the receptor, acting as an "off-switch".
Ang-2 binds to and occupies the Tie2 receptor without activation. This action competitively inhibits Ang-1 activity on the Tie2 receptor.