Bevacizumab cured age-related macular degeneration (AMD) via down-regulate TLR2 pathway

Abstract

Bevacizumab cured age-related macular degeneration (AMD) via down-regulate TLR2 pathway Abbreviations AMD -Age-related macular degeneration RPE -Retinal pigment epithelium TLR2 -The mammalian toll like receptor 2 P3C -Pam3CSK4 IntroductionAge-related macular degeneration (AMD) is the most common cause of blindness and visual impairment in people over 50 years of age [1,2]. During the pathological progress of AMD, retinal pigment epithelium (RPE) plays a very important role in choroidal neovascularisation (CNV, also called wet AMD) for atrophy of the PRE resulting from deposits called drusen that form between the retinal pigment epithelium (RPE) and underlying choroid [3]. To date, it is commonly proposing that oxidative damage is involving in RPE dysfunction in AMD, leading to subepithelial deposits and inflammation in RPE/choroid interface [4][5][6]. However, further studies on the mechanism of RPE dysfunction in AMD are required. Bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) is a full-length humanized anti-VEGF monoclonal IgG1 antibody (molecular weight 149 kDa) that inhibited the action of all isoforms of vascular endothelial growth factor. The drug was initially developed as an intravenous agent in the treatment of metastatic colorectal cancer [5]. In recent years, clinical trials have established the efficacy of Bevacizumab for the treatment of AMD [5,6]. Bevacizumab injections with 1.25 mg in a six weekly variable retreatment regimen are superior to standard care (pegaptanib sodium, verteporfin, sham). And then this treatment improved visual acuity on average at 54 weeks [2]. Furthermore, some groups Keywords: Bevacizumab • AMD • TLR2 • RPEAbstract: AMD is the main cause of visual impairment in people over 50 years of age and the most common cause of blindness. In recent years, the use of bevacizumab to treat neovascular AMD has become a preferred treatment in the United States. However, whether bevacozumab is available for RPE or AMD patients is unknown. We firstly indicate that Pam3CSK4 (P3C) activates TLR2 pathway during ARPE-19 apoptosis as determined by western blotting. And then, the expression of MyD88, NF-κB, p-IKK in primary RPE cells from AMD patients is significantly down-regulated after treatment with 50 μg L -1 Bevacizumab. Therefore, our data shows that MyD88 is involved in the TLR2 pathway in ARPE-19 cell apoptosis resulting from Pam3CSK4 (P3C). And more importantly, our findings suggested that Bevacizumab cured age-related macular degeneration (AMD) via down-regulate Toll-like receptor 2 (TLR2) pathway in RPE from AMD patients. © Versita Sp. z o.o.Brought to you by | MIT Libraries Authenticated Download Date | 5/11/18 12:11 AM