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Xinlei Wang, Eric Miller, Mayank Goswami, Robert J Zawadzki, Marie E Burns; IL6 Signaling in acute retinal detachment: Anti-inflammatory or Neuroprotective?. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5382.
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© ARVO (1962-2015); The Authors (2016-present)
Interleukin-6 has been implicated in most vitreoretinal diseases, but its role is unclear because IL6 can be both a pro- and anti-inflammatory cytokine. Retinal detachment (RD) elevates IL6 levels in a manner correlated with the extent of the detachment and the resulting retinal atrophy. Here we determined the time course and identity of the primary immune cells responding to acute RD in mice, and tested whether IL6 signaling following RD is anti-inflammatory or neuroprotective.
RD was induced in wild-type and IL6-deficient mice by subretinal injection of sodium hyaluronate. The RD location, extent and evolution was monitored longitudinally in-vivo by optical coherence tomography (OCT) imaging. The numbers and morphology of microglia (Iba1(hi), Cd11b(lo)) and monocytes (Iba1-, Cd11b(hi)) were assessed by flow cytometry and immunohistochemistry. Photoreceptor death and retinal atrophy was quantified by Tunel staining and retinal thickness measurement using optical coherence tomography. To prevent IL6 signaling in wild-type mice, RD was preceeded by intravitreal injection of IL6 receptor α (IL6Rα) antibody or IL6 receptor β (gp130) antibody.
All RD groups showed increased numbers of monocytes and resident microglia above control levels within 1 day after RD. Diffuse infiltration of monocytes was found in vitreous, nerve fiber layer and inner plexiform layer, while ameboid microglial cells populated the outer retinal layers. Retinal atrophy followed RD in all groups in days 3-7, and was found to be worse in both IL6-KO mice and following IL6Rα inhibition. However, blocking gp130 function reduced acute monocyte recruitment and photoreceptor death.
Monocytes infiltrate surprisingly rapidly following retinal detachment. These studies suggest the neuroprotective role of IL6 signaling in retinal detachment may be through IL6Rα, while more destructive cytokines coincidently signal through the soluble receptor gp130. Thus, future work more specifically targeting gp130 signaling may prove beneficial in mitigating the damaging consequences of neuroinflammation.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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