Role of α7 Nicotinic Acetylcholine Receptor and Protein Kinase C in Rat Retinal Ganglion Cell Survival In Vitro

Authors:
Publisher website
Google Scholar
Abstract
Retinal ganglion cell (RGC) death profoundly impacts vision because RGC axons form the optic nerve, which transmits information to central visual areas. The α7 nicotinic acetylcholine receptor (α7nAChR) participates in the cholinergic anti‐inflammatory pathway and plays a neuroprotective role in the central nervous system. Previously, we showed that protein kinase C activation by phorbol 12‐myristate 13‐acetate (PMA) treatment for 48 h increases the survival of neonatal rat RGCs by modulating muscarinic receptor levels. Herein, we aimed to investigate the effects of the selective α7nAChR agonist PNU‐282987 in rat retinal cell cultures and analyse whether the activation of this receptor is involved in PMA‐mediated RGC survival. Our results showed that α7nAChR inhibition using methyllycaconitine (MLA) abolished the effects of selected cholinergic agonists on RGC survival. We also observed that PNU‐282987 regulates TNF‐α and IL‐1β levels and release. Moreover, PNU‐282987 promoted RGC survival, and its neuroprotection was partially mediated by the induction of TNF‐α and IL‐1β during the initial stages of culture. MLA blocked the effect of PMA (50 ng/mL) on RGC, whereas PMA slightly increased the α7 subunit levels at 48 h. Further, PMA treatment decreased intracellular TNF‐α and p‐NF‐κB p50 levels through α7nAChR activation. In conclusion, we provide evidence that α7nAChR activation leads to the modulation of pro‐inflammatory cytokines in rat retinal cell cultures, thereby increasing RGC survival. Furthermore, activated α7nAChR enhances PKC activation and increases RGC survival after axotomy, corroborating the role of this receptor in neuroprotection.
Funding Information
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
  • Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação

This publication has 40 references indexed in Scilit: