2024-03-29T08:52:31Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00022894
2023-01-16T05:05:54Z
499:500:501
Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration
Ye, Fuxiang
67354
Kaneko, Hiroki
67355
Hayashi, Yumi
67356
Takayama, Kei
67357
Hwang, Shiang-Jyi
67358
Nishizawa, Yuji
67359
Kimoto, Reona
67360
Nagasaka, Yosuke
67361
Tsunekawa, Taichi
67362
Matsuura, Toshiyuki
67363
Yasukawa, Tsutomu
67364
Kondo, Takaaki
67365
Terasaki, Hiroko
67366
Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy–lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels.
journal article
Elsevier
2016-05
application/pdf
Free Radical Biology and Medicine
94
121
134
http://doi.org/10.1016/j.freeradbiomed.2016.02.027
http://hdl.handle.net/2237/25073
0891-5849
https://nagoya.repo.nii.ac.jp/record/22894/files/Manuscript_FY20160219_re-review_Clean.pdf
eng
https://doi.org/10.1016/j.freeradbiomed.2016.02.027
© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/