Explore additional resources of interest
Hear from the experts as they discuss the Ang–Tie pathway and its importance in retinal diseases.
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building on existing foundations
Dr. Patricio G. Schlottmann
Dr. Charles Wykoff
Prof. Anat Loewenstein
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Dr. Pipsa Saharinen
University of Helsinki
Helsinki, Finska
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Dr. Patricio G. Schlottmann
Organización Médica de Investigación
Buenos Aries, Argentina
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Ang-1 versus Ang-2
Prof. Anat Loewenstein
Tel Aviv Medical Center
Tel Aviv, Israel
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Explore the evidence
Dr. Charles Wykoff
Retina Consultants of Houston
Houston, Teksas, USA
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Dr. Stephan Michels
Augenklinik Zürich West and University of Zurich
Zurich, Switzerland
Embark on an animated journey to discover the role of angiopoietins and vascular instability in DME and nAMD.
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An animated journey
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Learn more about the role of angiopoietins in vascular stability and retinal disease.
Find answers to common questions related to angiopoietins and retinal 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
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
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
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
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).
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.5
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.6
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.7
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.7
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.8
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.9
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.
Reference:
- Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/retinal-diseases/symptoms-causes/syc-20355825
- Genentech. https://www.gene.com/patients/disease-education/age-related-macular-degeneration
- NEI. Dijabetička retinopatija https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy
- ASRS. https://www.asrs.org/patients/retinal-diseases/24/branch-retinal-vein-occlusion
- American Academy of Ophthalmology. https://www.aao.org/eye-health/diseases/what-is-central-retinal-veinocclusion
- 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. https://eyewiki.org/Choroidal_Neovascularization%3A_OCT_Angiography_Findings
- University of Michigan Kellogg Eye Institute. http://kellogg.umich.edu/theeyeshaveit/opticfundus/retinal_neovascularization.htm
- Scheppke L, et al. J Clin Invest. 2008.;118(6):2237.–46.