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Expert perspectives videos
Hear from the experts as they discuss the Ang–Tie pathway and its importance in retinal diseases.
Introduction to angiopoietins
Pipsa Saharinen, PhD
University of Helsinki,
Vascular stability: What is it
Patricio G. Schlottmann, MD
Organización Médica de Investigación,
Buenos Aires, Argentina
Learn more about the role of angiopoietins in vascular stability and retinal disease.
Angiopoietins: Key regulators of vascular stability
Download a detailed illustration showing how Ang-1 and Ang-2 promote vascular stability or instability.
A closer look at vascular stability
Download a visual summary of how Ang-1 and Ang-2 regulate vascular stability.
Find answers to common questions related to angiopoietins and retinal diseases.
What are retinal and choroidal diseases?
Retinal and choroidal diseases vary widely, but most of them cause visual symptoms. Retinal and choroidal diseases (i.e. age-related macular degeneration, diabetic retinopathy, diabetic macular edema, and retinal vein occlusion) can affect any part of your retina, a thin layer of tissue on the inside back wall of your eye.1
What is age-related macular degeneration?
Macular degeneration results from damage to the macula, the part of the retina needed for central vision and for seeing fine details clearly. Most cases occur as part of the aging process and are known as age-related macular degeneration (AMD).2
What is diabetic retinopathy?
Diabetic retinopathy (DR) is the most common cause of vision loss and blindness in people who have diabetes. DR is a consequence of long-term high blood sugar levels that cause damage to the small blood vessels in the retina.3
What is diabetic macular edema?
Diabetic macular edema (DME) occurs when the damaged blood vessels in the retina bleed and leak fluid, causing swelling (known as edema) around the macula. Over time, ~50% of people with DR will develop DME.3
What is retinal vein occlusion?
Retinal vein occlusions (RVO) occur when there is a blockage in the veins carrying blood away from the nerve cells in the retina.4 When the vein is blocked, blood and fluid spill out into the retina. The macula can swell from this fluid, affecting central vision. Eventually, without blood circulation, nerve cells in the eye can die and cause more vision loss.5
Depending on the location of the obstruction, RVO can be classified as central retinal vein occlusion (CRVO), hemiretinal vein occlusion (HRVO), or branch retinal vein occlusion (BRVO).6
What are angiopoietins?
Angiopoietins have been identified as a family of growth factors that are essential for blood vessel formation. There are four angiopoietins known as: angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), angiopoietin-3 (Ang-3), and angiopoietin-4 (Ang-4). The best-characterised angiopoietins are Ang-1 and Ang-2. The angiopoietins are all ligands for the Tie2 receptor.7
What is vascular stability?
In healthy blood vessels, vascular stability is established through appropriate levels and ratios of pro- and anti-angiogenic and inflammatory factors, including angiopoietins and VEGF, maintaining a state of homeostasis.8
What is vascular instability?
Under pathologic conditions, an angiogenic switch occurs, shifting the balance of pro- and anti-angiogenic and inflammatory factors. The upregulation of Ang-2 and VEGF, and the resultant Ang-2–Tie2 signalling, are causes of vascular instability, characterised by the leakage of vascular fluid into tissues, neovascularisation, and inflammation.8
What is choroidal neovascularisation?
Choroidal neovascularisation (CNV) is growth of new blood vessels from the choroid underlying the retinal pigment epithelium (RPE) and is accompanied by subretinal and intraretinal fluid, or sub-RPE vascular leakage and haemorrhage.9
What is retinal neovascularisation?
Retinal neovascularisation is defined as a state in which new pathologic blood vessels originate from the existing retinal veins and extend across the retinal surface.10
What is retinal vascular leakage?
Retinal vascular leakage is characterised by an increased vascular permeability accompanied by extravasation of fluids and proteins resulting in edema and is a leading cause of vision loss in diabetic retinopathy and retinal vascular occlusions. The VEGF pathway is known to have a key role in vascular permeability. In retinal diseases, VEGF-induced vascular leakage is likely related to loss of integrity in adherens junctions, which regulate cell-to-cell adhesion.11
AMD, age-related macular degeneration; Ang, angiopoietin; CNV, choroidal neovascularisation; DME, diabetic macular edema; DR, diabetic retinopathy; nAMD, neovascular age-related macular degeneration; RPE, retinal pigment epithelium; RVO, retinal vein occlusion; Tie, tyrosine kinase with immunoglobulin-like domains; VEGF, vascular endothelial growth factor.
- Mayo Clinic. Retinal diseases. https://www.mayoclinic.org/diseases-conditions/retinal-diseases/symptoms-causes/syc-20355825 [last accessed June 2022]
- Genentech. Age-related macular degeneration. https://www.gene.com/patients/disease-education/age-related-macular-degeneration [last accessed June 2022]
- NEI. Diabetic retinopathy. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy [last accessed June 2022]
- ASRS. Branch retinal vein occlusion. https://www.asrs.org/patients/retinal-diseases/24/branch-retinal-vein-occlusion [last accessed June 2022]
- American Academy of Ophthalmology. What is central retinal vein occlusion? https://www.aao.org/eye-health/diseases/what-is-central-retinal-vein-occlusion [last accessed June 2022]
- The Royal College of Ophthalmologists. Retinal vein occlusion guidelines. https://www.rcophth.ac.uk/wp-content/uploads/2015/07/Retinal-Vein-Occlusion-Guidelines-2022.pdf [last accessed June 2022]
- Thomas M, et al. Angiogenesis. 2009;12:125–37
- Saharinen P, et al. Nat Rev Drug Discov. 2017;16:635–61
- American Academy of Ophthalmology. Choroidal neovascularization: OCT angiography findings. https://eyewiki.org/Choroidal_Neovascularization%3A_OCT_Angiography_Findings [last accessed June 2022]
- University of Michigan Kellogg Eye Institute. Retinal vascularization. http://kellogg.umich.edu/theeyeshaveit/opticfundus/retinal_neovascularization.html [last accessed June 2022]
- Scheppke L, et al. J Clin Invest. 2008;118:2237–46