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Inhibition of LPS-Induced Retinal Microglia Activation by Naloxone Does Not Prevent Photoreceptor Death

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Abstract

Microglia-associated inflammation is closely related to the pathogenesis of retinal degenerative disorders. We have previously shown in vivo that naloxone protected photoreceptors from light-induced apoptosis possibly through inhibiting microglial activation. In this study, we attempted to explore the effect of lipopolysaccharide (LPS)-activated microglia on photoreceptor death and the influence of naloxone treatment using an in vitro retinal microglia and 661 W photoreceptor co-culture system. Immunofluorescent staining and ELISA measurements demonstrated that LPS activated microglia by changing the morphology and increasing the production of proinflammatory factors interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Flow cytometry analysis of annexin V/propidium iodide staining showed that LPS-activated microglia promoted the apoptosis of co-cultured 661 W photoreceptor cells. Naloxone inhibited microglial activation and decreased the release of IL-1beta and TNF-alpha but could not prevent photoreceptors from undergoing apoptosis. Considering the dual role of microglia-associated inflammation in both neurotoxicity and neuroprotection, modulating the function, rather than simply inhibiting their activation, might be a new therapeutic method for preventing photoreceptor degeneration.

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ACKNOWLEDGMENTS

This work was supported by research grants from the National Natural Science Foundation for the Young Scholars of China (no. 30901641), Shanghai Rising-Star Program (no. 10QA1401200), Young Talents Program of Shanghai Health System (no. XYQ2011058), and the National Natural Science Foundation (no. 81170857/H1205).

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Authors and Affiliations

  1. Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fen Yang Road, Shanghai, 200031, People’s Republic of China

    Xiaoshuang Jiang, Yingqin Ni, Meng Zhang, Hui Ren & Gezhi Xu

  2. Institute of Biochemistry, Chinese Academy of Science, Shanghai, People’s Republic of China

    Tianjin Liu

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  1. Xiaoshuang Jiang
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  2. Yingqin Ni
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Correspondence to Yingqin Ni or Gezhi Xu.

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Jiang, X., Ni, Y., Liu, T. et al. Inhibition of LPS-Induced Retinal Microglia Activation by Naloxone Does Not Prevent Photoreceptor Death. Inflammation 36, 42–52 (2013). https://doi.org/10.1007/s10753-012-9518-6

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