N-3 fatty acid and its metabolite 18-HEPE ameliorate retinal neuronal cell dysfunction by enhancing Müller BDNF in diabetic retinopathy

Ayana Suzumura, Hiroki Kaneko, Yasuhito Funahashi, Kei Takayama, Masatoshi Nagaya, Seina Ito, Toshiaki Okuno, Toshiaki Hirakata, Norie Nonobe, Keiko Kataoka, Hideyuki Shimizu, Rina Namba, Kazuhisa Yamada, Fuxiang Ye, Yoko Ozawa, Takehiko Yokomizo, Hiroko Terasaki

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H2O2) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H2O2 by high glucose, and H2O2 reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.

Original languageEnglish
Pages (from-to)724-735
Number of pages12
JournalDiabetes
Volume69
Issue number4
DOIs
Publication statusPublished - 2020 Apr 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'N-3 fatty acid and its metabolite 18-HEPE ameliorate retinal neuronal cell dysfunction by enhancing Müller BDNF in diabetic retinopathy'. Together they form a unique fingerprint.

  • Cite this

    Suzumura, A., Kaneko, H., Funahashi, Y., Takayama, K., Nagaya, M., Ito, S., Okuno, T., Hirakata, T., Nonobe, N., Kataoka, K., Shimizu, H., Namba, R., Yamada, K., Ye, F., Ozawa, Y., Yokomizo, T., & Terasaki, H. (2020). N-3 fatty acid and its metabolite 18-HEPE ameliorate retinal neuronal cell dysfunction by enhancing Müller BDNF in diabetic retinopathy. Diabetes, 69(4), 724-735. https://doi.org/10.2337/db19-0550