• Eun Kyoung Lee, Young Joo Kim, Won-Jun Shon, and Hyeong Gon Yu.
• Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
• Transl Res. 2020 Feb 1; 216: 30-42.

AbstractGV1001, a novel peptide derived from human telomerase reverse transcriptase, reportedly has anticancer and anti-inflammatory effects. Choroidal neovascularization (CNV) is a complex pathogenic process that involves angiogenesis, inflammation, cellular immunity, and other factors. This study was aimed at investigating the effect of GV1001 on laser-induced CNV in a rat model. Brown Norway rats were subcutaneously administered GV1001 (0.1 nM, 1 nM, and 10 nM) daily, beginning 3 days prior, and ending 14 days after laser photocoagulation. Optical coherence tomography, fluorescein angiography, choroidal flat mount, and histologic analysis were performed to analyze CNV. The protein level of IκB-α and nuclear translocation of nuclear factor κB (NF-κB) was analyzed via immunohistochemistry of p65. Multiplex immunoassay was performed to evaluate the interleukin (IL)-1β, IL-6, vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and tumor necrosis factor-α levels. The GV1001-treated group had significantly lower CNV thickness, smaller CNV area, and lower proportion of CNV lesions with clinically significant fluorescein leakage than vehicle-treated group. GV1001 treatment inhibited IκB-α degradation and NF-κB p65 nuclear translocation. At 1 nM concentration, GV1001 had highest inhibitory effect on CNV and NF-κB signaling activation; moreover, it suppressed the levels of IL-1β, IL-6, and VEGF significantly. The present study demonstrates that GV1001 treatment led to significant suppression of laser-induced CNV, alongside inhibition of inflammatory processes including NF-κB activation and subsequent upregulation of proinflammatory cytokines. Therefore, this provides molecular evidence of potential validity of GV1001 treatment as a therapeutic strategy for neovascular age-related macular degeneration.Copyright © 2019 Elsevier Inc. All rights reserved.

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