A telomerase-derived peptide vaccine inhibits laser-induced choroidal neovascularization in a rat model

Eun Kyoung Lee, Young Joo Kim, Won Jun Shon, Hyeong Gon Yu

Research output: Contribution to journalArticle

Abstract

GV1001, 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.

Original languageEnglish
Pages (from-to)30-42
Number of pages13
JournalTranslational Research
Volume216
DOIs
StatePublished - Feb 2020

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Choroidal Neovascularization
Subunit Vaccines
Telomerase
Rats
Lasers
Fluorescein
Interleukin-1
Vascular Endothelial Growth Factor A
Interleukin-6
Chemical activation
Angiography
Chemokine CCL2
Optical tomography
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Cytokines
Degradation
Peptides
Fluorescein Angiography
Light Coagulation

Cite this

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title = "A telomerase-derived peptide vaccine inhibits laser-induced choroidal neovascularization in a rat model",
abstract = "GV1001, 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.",
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A telomerase-derived peptide vaccine inhibits laser-induced choroidal neovascularization in a rat model. / Lee, Eun Kyoung; Kim, Young Joo; Shon, Won Jun; Yu, Hyeong Gon.

In: Translational Research, Vol. 216, 02.2020, p. 30-42.

Research output: Contribution to journalArticle

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