Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 51, Issue 2, Pages 493-502Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-013-0017-5
Keywords
PACAP; NMDA; Retinoprotection; Neurotrophic factor; Microglia/macrophage; Glaucoma
Categories
Funding
- MEXT-Support Program for the Strategic Research Foundation at Showa University
- [KAKENHI: 23249079]
- [24592681]
- [24592680]
- Grants-in-Aid for Scientific Research [25461333] Funding Source: KAKEN
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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/MI broken vertical bar) 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/MI broken vertical bar 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/MI broken vertical bar. 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/MI broken vertical bar. These results suggest that PACAP enhances the proliferation and/or infiltration of retinal MG/MI broken vertical bar and modulates their status into an acquired deactivation subtype to favor conditions for neuroprotection.
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