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

Autor: Taichi Tsunekawa, Yosuke Nagasaka, Yumi Hayashi, Tsutomu Yasukawa, Reona Kimoto, Toshiyuki Matsuura, Hiroki Kaneko, Shiang-Jyi Hwang, Kei Takayama, Hiroko Terasaki, Fuxiang Ye, Takaaki Kondo, Yuji Nishizawa
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Vascular Endothelial Growth Factor A
0301 basic medicine
medicine.medical_specialty
Patients
genetic structures
Swine
Retinal Pigment Epithelium
Biology
medicine.disease_cause
Biochemistry
Lipid peroxidation
Macular Degeneration
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Malondialdehyde
Physiology (medical)
Internal medicine
Autophagy
medicine
Animals
Humans
skin and connective tissue diseases
Retinal pigment epithelium
Macular degeneration
medicine.disease
Choroidal Neovascularization
eye diseases
Vascular endothelial growth factor
Oxidative Stress
Vascular endothelial growth factor A
030104 developmental biology
Endocrinology
Choroidal neovascularization
medicine.anatomical_structure
Gene Expression Regulation
chemistry
Fatty Acids
Unsaturated
030221 ophthalmology & optometry
Lipid Peroxidation
sense organs
medicine.symptom
Oxidative stress
Zdroj: Free Radical Biology and Medicine. 94:121-134
ISSN: 0891-5849
Popis: 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.
Databáze: OpenAIRE
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