STAT3 activation in circulating monocytes contributes to neovascular age-related macular degeneration

Mei Chen, J Lechner, J Zhao, L Toth, R Hogg, G Silvestri, A Kissenpfennig, U Chakravarthy, H Xu

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular age-related macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14+CD16-), non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre+/-:SOCS3fl/fl mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laser-induced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD.

Original languageEnglish
Pages (from-to)412-423
Number of pages12
JournalCurrent Molecular Medicine
Volume16
Issue number4
DOIs
Publication statusPublished - 24 Mar 2016

Fingerprint Dive into the research topics of 'STAT3 activation in circulating monocytes contributes to neovascular age-related macular degeneration'. Together they form a unique fingerprint.

  • Cite this