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Free Radic Biol Med. 2016 May;94:121-34. doi: 10.1016/j.freeradbiomed.2016.02.027. Epub 2016 Feb 23.

Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration.

Author information

1
Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
2
Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: h-kaneko@med.nagoya-u.ac.jp.
3
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya 461-8673, Japan; Institute for Advanced Research, Nagoya University, Nagoya 464-8601, Japan.
4
Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Laboratory of Bell Research Center-Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
5
Department of Biomedical Sciences, Chubu University, Kasugai, Aichi 487-8501, Japan.
6
Department of Ophthalmology, Nagoya City University School of Medicine, Nagoya 467-8601, Japan.
7
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya 461-8673, Japan.

Abstract

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.

KEYWORDS:

Age-related macular degeneration; Autophagy; Linoleic acid; Lipid peroxidation; Malondialdehyde

[Indexed for MEDLINE]

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