PACAP Attenuates NMDA-Induced Retinal Damage in Association with Modulation of the Microglia/Macrophage Status into an Acquired Deactivation Subtype.

Wada, Y; Nakamachi, T; Endo, K; Seki, T; Ohtaki, H; Tsuchikawa, D; Hori, M; Tsuchida, M; Yoshikawa, A; Matkovits, A [Matkovits, Attila (PhD Orvostudomány), szerző] Anatómiai Intézet (PTE / ÁOK); Kagami, N; Imai, N; Fujisaka, S; Usui, I; Tobe, K; Koide, R; Takahashi, H; Shioda, S

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
  • SJR Scopus - Medicine (miscellaneous): Q1
Azonosítók
Szakterületek:
    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/MPhi) 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/MPhi 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/MPhi. 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/MPhi. These results suggest that PACAP enhances the proliferation and/or infiltration of retinal MG/MPhi and modulates their status into an acquired deactivation subtype to favor conditions for neuroprotection.
    Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSL
    2019-12-05 18:25