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Updated: Feb 27, 2026
Experimental Models for Study of Retinal Pigment Epithelial Physiology and Pathophysiology
Published on: November 6, 2010
Rapid monocyte infiltration following retinal detachment is dependent on non-canonical IL6 signaling through gp130
Xinlei Wang1,2, Eric B Miller3, Mayank Goswami2,4
1Department of Ophthalmology & Vision Science, University of California, Davis, USA.
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.
Insights
Monocytes drive the cytokine storm after retinal detachment (RD). Blocking gp130, not IL6, inhibits monocyte infiltration, suggesting new therapies for preventing vision loss from proliferative vitreoretinopathy (PVR).
Area of Science:
- Ophthalmology
- Immunology
- Retinal Biology
Background:
- Retinal detachment (RD) can lead to proliferative vitreoretinopathy (PVR), a major cause of irreversible vision loss.
- PVR involves a cytokine storm, but the source and signaling of key molecules like IL6 remain unclear.
- Understanding the early immune response to RD is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the early immune cell response following RD in a mouse model.
- To identify the source and downstream signaling pathways of IL6 in the context of RD.
- To explore potential therapeutic targets for preventing PVR.
Main Methods:
- RD was induced in C57BL/6J and IL6 knockout mice.
- Immunohistochemistry and flow cytometry assessed inflammatory responses.
- Cytokine arrays, Western blotting, and intravitreal injections of blocking antibodies (IL6Rα or gp130) were employed.
Main Results:
- Bone marrow-derived monocytes infiltrated the vitreous within one day of RD, while retinal microglia remained largely unaffected.
- IL6 signaling was activated in the vitreous and aqueous humor, not the neurosensory retina.
- Blocking gp130 inhibited monocyte infiltration, whereas IL6 knockout or IL6Rα blockade did not.
Conclusions:
- Monocytes are the primary immune cells mediating the cytokine storm after RD.
- Retinal damage is likely due to gp130-mediated signaling in monocytes, not direct IL6 retinal signaling.
- Immediate RD treatment and gp130-targeted therapies may prevent PVR and enhance retinal healing.
