The angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) pathway is an emerging key regulator in vascular development and maintenance. Its relevance to clinicians and basic scientists as a potential therapeutic target in retinal and choroidal vascular diseases is highlighted by recent preclinical and clinical evidence. The Ang/Tie pathway plays an important role in the regulation of vascular stability, in angiogenesis under physiological and pathological conditions, as well as in inflammation. Under physiological conditions, angiopoietin-1 (Ang-1) binds to and phosphorylates the Tie2 receptor, leading to downstream signalling that promotes cell survival and vascular stability. Angiopoietin-2 (Ang-2) is upregulated under pathological conditions and acts as a context-dependent agonist/antagonist of the Ang-1/Tie2 axis, causing vascular destabilisation and sensitising blood vessels to the effects of vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A synergistically drive vascular leakage, neovascularisation and inflammation, key components of retinal vascular diseases. Preclinical evidence suggests that modulating the Ang/Tie pathway restores vascular stabilisation and reduces inflammation. This review discusses how targeting the Ang/Tie pathway or applying Ang-2/VEGF-A combination therapy may be a valuable therapeutic strategy for restoring vascular stability and reducing inflammation in the treatment of retinal and choroidal vascular diseases.

Joussen, A.m., Ricci, F., Paris, L.p., Korn, C., Quezada-Ruiz, C., Zarbin, M. (2021). Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data. EYE, 35(5), 1305-1316 [10.1038/s41433-020-01377-x].

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Ricci F.
Conceptualization
;
2021-01-01

Abstract

The angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) pathway is an emerging key regulator in vascular development and maintenance. Its relevance to clinicians and basic scientists as a potential therapeutic target in retinal and choroidal vascular diseases is highlighted by recent preclinical and clinical evidence. The Ang/Tie pathway plays an important role in the regulation of vascular stability, in angiogenesis under physiological and pathological conditions, as well as in inflammation. Under physiological conditions, angiopoietin-1 (Ang-1) binds to and phosphorylates the Tie2 receptor, leading to downstream signalling that promotes cell survival and vascular stability. Angiopoietin-2 (Ang-2) is upregulated under pathological conditions and acts as a context-dependent agonist/antagonist of the Ang-1/Tie2 axis, causing vascular destabilisation and sensitising blood vessels to the effects of vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A synergistically drive vascular leakage, neovascularisation and inflammation, key components of retinal vascular diseases. Preclinical evidence suggests that modulating the Ang/Tie pathway restores vascular stabilisation and reduces inflammation. This review discusses how targeting the Ang/Tie pathway or applying Ang-2/VEGF-A combination therapy may be a valuable therapeutic strategy for restoring vascular stability and reducing inflammation in the treatment of retinal and choroidal vascular diseases.
2021
Pubblicato
Rilevanza internazionale
Review
Esperti anonimi
Settore MED/30 - MALATTIE APPARATO VISIVO
Settore MEDS-17/A - Malattie dell'apparato visivo
English
Humans
Receptor, TIE-2
Signal Transduction
Vascular Endothelial Growth Factor A
Angiopoietins
Vascular Diseases
Joussen, A.m., Ricci, F., Paris, L.p., Korn, C., Quezada-Ruiz, C., Zarbin, M. (2021). Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data. EYE, 35(5), 1305-1316 [10.1038/s41433-020-01377-x].
Joussen, Am; Ricci, F; Paris, Lp; Korn, C; Quezada-Ruiz, C; Zarbin, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/286149
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