TY - JOUR
T1 - N-3 fatty acid and its metabolite 18-HEPE ameliorate retinal neuronal cell dysfunction by enhancing Müller BDNF in diabetic retinopathy
AU - Suzumura, Ayana
AU - Kaneko, Hiroki
AU - Funahashi, Yasuhito
AU - Takayama, Kei
AU - Nagaya, Masatoshi
AU - Ito, Seina
AU - Okuno, Toshiaki
AU - Hirakata, Toshiaki
AU - Nonobe, Norie
AU - Kataoka, Keiko
AU - Shimizu, Hideyuki
AU - Namba, Rina
AU - Yamada, Kazuhisa
AU - Ye, Fuxiang
AU - Ozawa, Yoko
AU - Yokomizo, Takehiko
AU - Terasaki, Hiroko
N1 - Publisher Copyright:
© 2020 by the American Diabetes Association.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db19-0550
DO - 10.2337/db19-0550
M3 - Article
C2 - 32029482
AN - SCOPUS:85082146599
SN - 0012-1797
VL - 69
SP - 724
EP - 735
JO - Diabetes
JF - Diabetes
IS - 4
ER -