Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration

Mihoko Suzuki, Motokazu Tsujikawa, Hiroyuki Itabe, Zhao Jiang Du, Ping Xie, Nagakazu Matsumura, Xiaoming Fu, Renliang Zhang, Kohei Sonoda, Kensuke Egashira, Stanley L. Hazen, Motohiro Kamei

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD.

Original languageEnglish
Pages (from-to)2407-2415
Number of pages9
JournalJournal of Cell Science
Volume125
Issue number10
DOIs
Publication statusPublished - Aug 14 2012

Fingerprint

Macular Degeneration
Oxidative Stress
Phospholipids
Chemokine CCL2
Choroidal Neovascularization
Inflammation
Light
CC Chemokines
Blindness
Developed Countries
Retina
Antioxidants
Macrophages
Pathology
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Suzuki, M., Tsujikawa, M., Itabe, H., Du, Z. J., Xie, P., Matsumura, N., ... Kamei, M. (2012). Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration. Journal of Cell Science, 125(10), 2407-2415. https://doi.org/10.1242/jcs.097683

Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration. / Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Kohei; Egashira, Kensuke; Hazen, Stanley L.; Kamei, Motohiro.

In: Journal of Cell Science, Vol. 125, No. 10, 14.08.2012, p. 2407-2415.

Research output: Contribution to journalArticle

Suzuki, M, Tsujikawa, M, Itabe, H, Du, ZJ, Xie, P, Matsumura, N, Fu, X, Zhang, R, Sonoda, K, Egashira, K, Hazen, SL & Kamei, M 2012, 'Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration', Journal of Cell Science, vol. 125, no. 10, pp. 2407-2415. https://doi.org/10.1242/jcs.097683
Suzuki, Mihoko ; Tsujikawa, Motokazu ; Itabe, Hiroyuki ; Du, Zhao Jiang ; Xie, Ping ; Matsumura, Nagakazu ; Fu, Xiaoming ; Zhang, Renliang ; Sonoda, Kohei ; Egashira, Kensuke ; Hazen, Stanley L. ; Kamei, Motohiro. / Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration. In: Journal of Cell Science. 2012 ; Vol. 125, No. 10. pp. 2407-2415.
@article{a334d0a6c078462fb4dcfb7406f9bfcb,
title = "Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration",
abstract = "Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD.",
author = "Mihoko Suzuki and Motokazu Tsujikawa and Hiroyuki Itabe and Du, {Zhao Jiang} and Ping Xie and Nagakazu Matsumura and Xiaoming Fu and Renliang Zhang and Kohei Sonoda and Kensuke Egashira and Hazen, {Stanley L.} and Motohiro Kamei",
year = "2012",
month = "8",
day = "14",
doi = "10.1242/jcs.097683",
language = "English",
volume = "125",
pages = "2407--2415",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "10",

}

TY - JOUR

T1 - Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration

AU - Suzuki, Mihoko

AU - Tsujikawa, Motokazu

AU - Itabe, Hiroyuki

AU - Du, Zhao Jiang

AU - Xie, Ping

AU - Matsumura, Nagakazu

AU - Fu, Xiaoming

AU - Zhang, Renliang

AU - Sonoda, Kohei

AU - Egashira, Kensuke

AU - Hazen, Stanley L.

AU - Kamei, Motohiro

PY - 2012/8/14

Y1 - 2012/8/14

N2 - Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD.

AB - Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD.

UR - http://www.scopus.com/inward/record.url?scp=84864819030&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864819030&partnerID=8YFLogxK

U2 - 10.1242/jcs.097683

DO - 10.1242/jcs.097683

M3 - Article

VL - 125

SP - 2407

EP - 2415

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 10

ER -