Title:STAT3 Activation in Circulating Monocytes Contributes to Neovascular Age-Related Macular Degeneration
VOLUME: 16 ISSUE: 4
Author(s):M. Chen, J. Lechner, J. Zhao, L. Toth, R. Hogg, G. Silvestri, A. Kissenpfennig, U. Chakravarthy and H. Xu
Affiliation:Wellcome-Wolfson Institute of Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK., Wellcome-Wolfson Institute of Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
Keywords:Macrophage, monocyte, angiogenesis, retina, age-related macular degeneration, cytokine.
Abstract:Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular agerelated
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 laserinduced
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.
