STAT3的活化循环单核细胞促进新生血管性老年性黄斑变性

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, H. Xu

Affiliation:

关键词: 巨噬细胞，单核细胞，血管生成，视网膜，年龄相关性黄斑变性，细胞因子。

摘要: 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^+/-:SOCS3^fl/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.

Cite this article as:

M. Chen, J. Lechner, J. Zhao, L. Toth, R. Hogg, G. Silvestri, A. Kissenpfennig, U. Chakravarthy, H. Xu , STAT3 Activation in Circulating Monocytes Contributes to Neovascular Age-Related Macular Degeneration, Current Molecular Medicine 2016; 16 (4) . https://dx.doi.org/10.2174/1566524016666160324130031