For US Healthcare Professionals

For US Healthcare Professionals

THE ANG-TIE PATHWAY PLAYS A ROLE IN
HEALTHY AND DISEASED EYES1

In the US, nAMD affects more than 1.1 million people and accounts for 90% of all AMD-related vision loss.7,8 Additionally, nearly 750,000 Americans have DME—the leading cause of blindness in people with diabetes.9,10 With the growing rate of lives impacted by these diseases, now is the time for deeper exploration.

Healthy eyes have an activated Ang-Tie pathway1,11,12

An activated Ang-Tie pathway regulates endothelial cell survival and maintains vascular stability and homeostasis.1,11,12 This pathway is activated when Ang-1 binds to the Tie2 receptors on endothelial cells.12,13

Medical illustration representing the endothelial cell under healthy conditions.
Experience the Ang-Tie pathway in action.
Eye-shaped icon accompanying content about vascular stability.

Ang-1 activates the Tie2 receptor, promoting the survival of endothelial cells and the stability of cell junctions. The result? Vascular stability.1,14

With diseased eyes, pathological stressors flip an angiogenic switch1,15-18

Stressors to the vascular system, like nAMD and DME, trigger an angiogenic switch that upregulates Ang-2 and VEGF. Once triggered, elevated Ang-2 outcompetes Ang-1. While the binding of VEGF-A to VEGFR-2 promotes the initiation of angiogenesis, inhibition of the Ang-Tie pathway by Ang-2 prevents maintenance of the vasculature.1,2,11,12

Medical illustration representing the endothelial cell under pathologic conditions.
Experience the Ang-Tie pathway in action.
Eye-shaped icon accompanying content about the difference between Ang-1-Tie2 and Ang-2-Tie2.

Ang-1–Tie2 signaling promotes retinal vascular stability maintaining homeostasis, whereas Ang-2–Tie2 signaling and VEGF may work together to drive vascular leakage, neovascularization, and inflammation.1,11

Elevated Ang-2 inhibits the Ang-Tie pathway—leading to vascular instability1,2

As Ang-2 and VEGF are upregulated, they continue to wreak havoc together by driving vascular instability (neovascularization, vascular leakage, and inflammation).1,11,15

First, Ang-2 causes the breakdown of the blood retinal barrier, increases in inflammation, and sensitizes the blood vessels to VEGF to further destabilize retinal blood vessels.2,19,20 From there, increased sensitization of the retinal vasculature to VEGF further exacerbates neovascularization and vascular leakage.1,21,22

Medical illustration representing the endothelial cell and the angiogenic switch.
Experience the Ang-Tie pathway in action.

AMD=age-related macular degeneration; Ang-1=angiopoietin-1; Ang-2=angiopoietin-2; Ang-Tie=angiopoietin/Tie; DME=diabetic macular edema; nAMD=neovascular age-related macular degeneration; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor.

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