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. 2013 Oct;51(2):493-502.
doi: 10.1007/s12031-013-0017-5. Epub 2013 May 30.

PACAP attenuates NMDA-induced retinal damage in association with modulation of the microglia/macrophage status into an acquired deactivation subtype

Yoshihiro Wada  1 , Tomoya Nakamachi, Kimi Endo, Tamotsu Seki, Hirokazu Ohtaki, Daisuke Tsuchikawa, Motohide Hori, Masashi Tsuchida, Akira Yoshikawa, Attila Matkovits, Nobuyuki Kagami, Nori Imai, Shiho Fujisaka, Isao Usui, Kazuyuki Tobe, Ryohei Koide, Haruo Takahashi, Seiji Shioda
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PACAP attenuates NMDA-induced retinal damage in association with modulation of the microglia/macrophage status into an acquired deactivation subtype

Yoshihiro Wada et al. J Mol Neurosci. 2013 Oct.

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been known as a neuroprotectant agent in several retinal injury models. However, a detailed mechanism of this effect is still not well understood. In this study, we examined the retinoprotective effects and associated underlying mechanisms of action of PACAP in the mouse N-methyl-D-aspartic acid (NMDA)-induced retinal injury model, focusing on the relationship between PACAP and retinal microglia/macrophage (MG/MΦ) status. Adult male C57BL/6 mice received an intravitreal injection of NMDA to induce retinal injury. Three days after NMDA injection, the number of MG/MΦ increased significantly in the retinas. The concomitant intravitreal injection of PACAP suppressed NMDA-induced cell loss in the ganglion cell layer (GCL) and significantly increased the number of MG/MΦ. These outcomes associated with PACAP were attenuated by cotreatment with PACAP6-38, while the beneficial effects of PACAP were not seen in interleukin-10 (IL-10) knockout mice. PACAP significantly elevated the messenger RNA levels of anti-inflammatory cytokines such as transforming growth factor beta 1 and IL-10 in the injured retina, with the immunoreactivities seen to overlap with markers of MG/MΦ. These results suggest that PACAP enhances the proliferation and/or infiltration of retinal MG/MΦ and modulates their status into an acquired deactivation subtype to favor conditions for neuroprotection.

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References

    1. J Mol Neurosci. 2011 Jan;43(1):51-7 - PubMed
    1. Arch Ophthalmol. 1996 Mar;114(3):299-305 - PubMed
    1. Nat Rev Immunol. 2008 Dec;8(12):958-69 - PubMed
    1. Trends Immunol. 2004 Dec;25(12):677-86 - PubMed
    1. Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5206-11 - PubMed

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