Vinpocetine inhibits amyloid-beta induced activation of NF-κB, NLRP3 inflammasome and cytokine production in retinal pigment epithelial cells

Chronic inflammation is a key pathogenic process in age-related macular degeneration (AMD). Amyloid-beta (A beta) is a constituent of AMD drusen and promotes the activation of NLRP3 inflammasome which facilitates the production of cytokines. We investigated the role of transcription factor NF-kappa B in the activation of inflammasome in the RPE and the effect of vinpocetine, a dietary supplement with inhibitory effect on NF-kappa B. ARPE19/NF-kappa B-luciferase reporter cells treated with All demonstrated enhanced NF-kappa B activation that was significantly suppressed by vinpocetine. Intraperitoneal injection of vinpocetine (15 mg/kg) inhibited NF-kappa B nuclear translocation and reduced the expression and activation of NLRP3, caspase-1, IL-1 beta, IL-18, and TNF-alpha in the RPE of adult rats that received intraocular A beta, as measured by retinal immunohistochemistry and Western blot. Cytokine level in the vitreous was assayed using multiplex suspension arrays and revealed significantly lower concentration of MIP-3 alpha, IL-6, IL-1 alpha, IL-1 beta, IL-18, and TNF-alpha in vinpocetine treated animals. These results suggest that the NF-kappa B pathway is activated by A beta in the RPE and signals the priming of NLRP3 inflammasome and the expression of pro-inflammatory cytokines including the inflammasome substrates IL-1 beta and IL-18. NF-kappa B inhibition may be an effective approach to stem the chronic inflammatory milieu that underlies the development of AMD. Vinpocetine is a potentially useful anti-inflammatory agent that is well-tolerated in long term use. (C) 2014 Elsevier Ltd. All rights reserved.