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

التفاصيل البيبلوغرافية
العنوان: PACAP Attenuates NMDA-Induced Retinal Damage in Association with Modulation of the Microglia/Macrophage Status into an Acquired Deactivation Subtype
المؤلفون: Tomoya Nakamachi, Seiji Shioda, Akira Yoshikawa, Tamotsu Seki, Hirokazu Ohtaki, Masashi Tsuchida, Ryohei Koide, Kazuyuki Tobe, Shiho Fujisaka, Kimi Endo, Motohide Hori, Nori Imai, Yoshihiro Wada, Haruo Takahashi, Nobuyuki Kagami, Attila Matkovits, Isao Usui, Daisuke Tsuchikawa
المصدر: Journal of Molecular Neuroscience. 51:493-502
بيانات النشر: Springer Science and Business Media LLC, 2013.
سنة النشر: 2013
مصطلحات موضوعية: Male, Retinal Ganglion Cells, endocrine system, medicine.medical_specialty, N-Methylaspartate, Biology, Neuroprotection, Retina, Transforming Growth Factor beta1, Mice, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Neurotrophic factors, Internal medicine, medicine, Animals, RNA, Messenger, Ganglion cell layer, Cell Proliferation, Microglia, Macrophages, Glaucoma, Retinal, General Medicine, Macrophage Activation, Interleukin-10, Mice, Inbred C57BL, Neuroprotective Agents, Endocrinology, medicine.anatomical_structure, chemistry, Intravitreal Injections, Knockout mouse, Pituitary Adenylate Cyclase-Activating Polypeptide, NMDA receptor, hormones, hormone substitutes, and hormone antagonists
الوصف: 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.
تدمد: 1559-1166
0895-8696
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::027a679112d4b164d9bbe0febcb55006
https://doi.org/10.1007/s12031-013-0017-5
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....027a679112d4b164d9bbe0febcb55006
قاعدة البيانات: OpenAIRE