June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Beneficial effect of fursultiamine on choroidal neovascularization: A potential blockade on metabolic reprogramming in inflammatory retinal pigment epithelium
Author Affiliations & Notes
  • Dong Ho Park
    Ophthalmology, Kyungpook National Univ Hospital, Daegu, Korea (the Republic of)
    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Juhee Kim
    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Ji Yeon Do
    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Mi-jin Kim
    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Ryoji Yanai
    Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Japan
  • In-Kyu Lee
    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Sungmi Park
    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Dong Ho Park, None; Juhee Kim, None; Ji Yeon Do, None; Mi-jin Kim, None; Ryoji Yanai, None; In-Kyu Lee, None; Sungmi Park, None
  • Footnotes
    Support  Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2017R1D1A1B03027966), funded by the Korean government (Ministry of Science and ICT) (2019R1A2C1084371), and the Korea Health Technology R&D Project of the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1501).
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 5396. doi:
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      Dong Ho Park, Juhee Kim, Ji Yeon Do, Mi-jin Kim, Ryoji Yanai, In-Kyu Lee, Sungmi Park; Beneficial effect of fursultiamine on choroidal neovascularization: A potential blockade on metabolic reprogramming in inflammatory retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5396.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To investigate the inhibitory effect of thiamine analogue on choroidal neovascularization (CNV) model, mediated by anti-inflammatory effect and mitochondrial respiration in human retinal pigment epithelium (RPE).

Methods : In laser induced CNV model, the effects of fursultiamine were assessed by the vascular leakage and CNV size. The inflammatory signaling was evaluated by qPCR, Western blot, and ELISA in both tissues and cells, which was measured by lactate production and oxygen consumption rate in LPS (endotoxin) treated APRE-19.

Results : Fursultiamine significantly reduced the vascular leakage and neovascular lesion size along with inflammatory cytokines including IL-1β, IL-6, IL-8, TNF-α, and MCP-1 in choroid and retina. These anti-inflammatory effects of fursultiamine were correlated with the reduced proinflammatory cytokines and phosphorylation of NF-κB in APRE-19. Interestingly, fursultiamine significantly enhanced the spare and maximal mitochondrial respiration correlated with the reduced lactate production compared to LPS only. Likewise, hypoxia induced lactate production and inhibitory phosphorylation of pyruvate dehydrogenase and mitochondrial fission which were attenuated by fursultiamine treatment.

Conclusions : Fursultiamine might be the therapeutics for neovascular age-related macular degeneration, validated by both anti-inflammatory responses and reduced metabolic reprogramming based on enhanced the oxidative phosphorylation in the mitochondria.

This is a 2020 ARVO Annual Meeting abstract.

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