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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Rapid monocyte infiltration following retinal detachment is dependent on non-canonical IL6 signaling through gp130

Authors: Xinlei Wang, Eric B. Miller, Mayank Goswami, Pengfei Zhang, Kaitryn E. Ronning, Sarah J. Karlen, Robert J. Zawadzki, Edward N. Pugh Jr., Marie E. Burns

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Retinal detachment (RD) can lead to proliferative vitreoretinopathy (PVR), a leading cause of intractable vision loss. PVR is associated with a cytokine storm involving common proinflammatory molecules like IL6, but little is known about the source and downstream signaling of IL6 and the consequences for the retina. Here, we investigated the early immune response and resultant cytokine signaling following RD in mice.

Methods

RD was induced in C57BL/6 J and IL6 knockout mice, and the resulting inflammatory response was examined using immunohistochemistry and flow cytometry. Cytokines and signaling proteins of vitreous and retinas were quantified by multiple cytokine arrays and Western blotting. To attempt to block IL6 signaling, a neutralizing antibody of IL6 receptor α (IL6Rα) or IL6 receptor β (gp-130) was injected intravitreally immediately after RD.

Results

Within one day of RD, bone marrow-derived Cd11b + monocytes had extravasated from the vasculature and lined the vitreal surface of the retina, while the microglia, the resident macrophages of the retina, were relatively unperturbed. Cytokine arrays and Western blot analysis revealed that this sterile inflammation did not cause activation of IL6 signaling in the neurosensory retina, but rather only in the vitreous and aqueous humor. Monocyte infiltration was inhibited by blocking gp130, but not by IL6 knockout or IL6Rα blockade.

Conclusions

Together, our results demonstrate that monocytes are the primary immune cell mediating the cytokine storm following RD, and that any resulting retinal damage is unlikely to be a direct result of retinal IL6 signaling, but rather gp130-mediated signaling in the monocytes themselves. These results suggest that RD should be treated immediately, and that gp130-directed therapies may prevent PVR and promote retinal healing.
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Metadata
Title
Rapid monocyte infiltration following retinal detachment is dependent on non-canonical IL6 signaling through gp130
Authors
Xinlei Wang
Eric B. Miller
Mayank Goswami
Pengfei Zhang
Kaitryn E. Ronning
Sarah J. Karlen
Robert J. Zawadzki
Edward N. Pugh Jr.
Marie E. Burns
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0886-6

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