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

Antonia M. Joussen, Federico Ricci, Liliana P. Paris, Claudia Korn, Carlos Quezada-Ruiz, Marco Zarbin

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1305-1316
Number of pages12
JournalEye (Basingstoke)
Volume35
Issue number5
DOIs
StatePublished - May 2021

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems

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