April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
STAT3 activation in circulating immune cells is related to neovascular age-related macular degeneration
Author Affiliations & Notes
  • Heping Xu
    Centre for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom
  • Judith Lecher
    Centre for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom
  • Usha Chakravarthy
    Centre for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom
  • Mei Chen
    Centre for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom
  • Footnotes
    Commercial Relationships Heping Xu, None; Judith Lecher, None; Usha Chakravarthy, None; Mei Chen, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 72. doi:
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    • Get Citation

      Heping Xu, Judith Lecher, Usha Chakravarthy, Mei Chen; STAT3 activation in circulating immune cells is related to neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):72.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The Signal Transducer and Activator of Transcription 3 (STAT3) pathway is known to play an important role in inflammation and angiogenesis. STAT3 can be activated by IL-6 family cytokines through the receptor IL-6R/gp130. Increased IL-6 has been detected in the plasma and vitreous in neovascular age-related macular degeneration (nAMD) patients. The aim of this study was to investigate the role of the STAT3 pathway in the pathogenesis of nAMD.

Methods: Blood cells from nAMD patients (n = 11) and age-, gender-matched healthy controls (n = 13) were stimulated with IL-6 for 20 minutes. The expression of the activated form of STAT3 (p-STAT3) was examined by flow cytometry. The mRNA levels of gp130, IL-6R and the suppressor of cytokine signalling 3 (SOCS3, a negative regulator of p-STAT3) were evaluated by real-time RT-PCR. Laser-induced choroidal neovascularisation (CNV) was performed in WT C57BL/6J mice as well as in the myeloid cell specific SOCS3 deficiency mice i.e., the LysMCre-SOCS3fl/fl mice. STAT3 activation in CNV lesions was examined by western blot. The size of CNV at different times after laser treatment was measured by confocal microscopy of RPE/choroidal flatmounts.

Results: The expression of p-STAT3 in CD11b+ monocytes was significantly increased in nAMD patients compared to healthy controls, although mRNA expression of gp130, IL-6R and SOCS3 did not differ between patients and controls. The expression of p-STAT3 in the retinal and RPE/choroidal tissues was increased at 1 and 3 days after laser treatment. The administration of a STAT3 inhibitor LLL12 significantly suppressed CNV. CD11b+ monocytes from LysMCre-SOCS3fl/fl mice expressed higher levels of p-STAT3 compared to the cells from WT mice. Laser induced CNV developed earlier and were larger in LysMCre-SOCS3fl/fl mice compared to WT C57BL/6J mice.

Conclusions: Our results suggest that STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD, and targeting the STAT3 pathway may have therapeutic potential in nAMD.

Keywords: 412 age-related macular degeneration • 557 inflammation • 739 transcription factors  
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