The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy

Jun Cai, Oksana Kehoe, Gill M. Smith, Philip Hykin, Michael E. Boulton

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Purpose. The angiopoietin (Ang) system plays an important role in vascular stabilization and pathologic neovascularization. The hypothesis for the study was that, in addition to modulating endothelial cell behavior, the angiopoietin/Tie-2 system also regulates the pericyte apoptosis and/or the vessel maturation associated with diabetic retinopathy. methods. Tie-2 expression in cultured retinal pericytes was analyzed by using ELISA, Western Blot analysis, and flow cytometry. CD13 (aminopeptidase N) expression in pericytes was determined by Western blot analysis and Ang effects verified with Tie-2 antisense treatment. Cell proliferation was monitored by crystal violet uptake, and pericyte migration was assessed in a scrape wound. Annexin V-FITC flow cytometry was used to quantify pericyte apoptosis. Results. Pericytes expressed a functionally active Tie-2 receptor upregulated by both Ang-1 and -2 (P <0.05). In pericytes undergoing apoptosis induced by either TNF-α or high glucose Ang-1 increased survival (P <0.05 for TNF-α P <0.01 for high glucose), whereas Ang-2 increased apoptosis. Ang-1 enhanced CD13 expression in a dose-dependent manner (P <0.05) and stimulated pericyte migration in a synthetic matrix wound- healing assay that was associated with a change in F-actin organization. Addition of Tie-2 antisense confirmed that angio- poietins act through Tie-2. onclusions. These findings demonstrate that Tie-2 is functional in pericytes and may play an important role in the progression of diabetic retinopathy, by regulating pericyte loss and influencing the activation state and recruitment of pericytes.

Original languageEnglish (US)
Pages (from-to)2163-2171
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number5
DOIs
StatePublished - Apr 2008
Externally publishedYes

Fingerprint

Angiopoietin-2
Pericytes
Diabetic Retinopathy
Angiopoietins
Angiopoietin-1
Apoptosis
Flow Cytometry
Western Blotting
Pathologic Neovascularization
Gentian Violet
CD13 Antigens
Glucose
Fluorescein-5-isothiocyanate
Annexin A5
Wound Healing
Blood Vessels
Actins

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. / Cai, Jun; Kehoe, Oksana; Smith, Gill M.; Hykin, Philip; Boulton, Michael E.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 5, 04.2008, p. 2163-2171.

Research output: Contribution to journalArticle

Cai, Jun ; Kehoe, Oksana ; Smith, Gill M. ; Hykin, Philip ; Boulton, Michael E. / The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 5. pp. 2163-2171.
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