Chronic Photo-oxidative Stress And Subsequent Mcp-1 Activation As Causative Factors For Age-related Macular Degeneration

Abstract

Purpose: : We previously reported that mild light irradiation induces phospholipids oxidation and, subsequently, an increase of MCP-1 secretion and accumulation of macrophages. The purpose of this study is to investigate whether chronic photo-oxidative stress is involved in the pathogenesis of age-related macular degeneration (AMD) as an environmental factor.

Methods: : Freely moving 12-month-old C57BL/6 wild mice were subjected to low-level blue-light irradiation (500 lux) every 2 days for 4 to 6 months. We performed fundus examination, fluorescein angiography, and electron microscopic and immunohistochemical examination. We also examined the difference of oxidized phospholipids and monocyte chemoattractant protein-1(MCP-1) by real-time PCR, ELISA and immunohistochemistry in acute blue-light irradiated mice (1000 lux) with daily injected antioxidant, α-Phenyl-N-tert-butylnitrone (PBN) treatment.

Results: : Choroidal neovascularization (CNV) was observed in 4 of 8 eyes (50%) in long term light irradiated mice, while the non-irradiated control mice showed no CNV (0%). Fluorescein angiography and histopathologic examinations revealed that the CNV was the occult-dominant type with a proliferated vascular tissue between the RPE and Bruch's membrane. Macrophages accumulation around the CNV and engulfing the photoreceptor outer segments, including the oxidized phospholipids, were revealed by the electron microscopic and immunohistochemical examinations. The increased oxidized phopholipids and MCP-1 mRNA and protein (p<0.001) after light irradiation were significantly decreased by the PBN treatment (p<0.05).

Conclusions: : The present study suggests that mild chronic photo-oxidative stress may be involved in AMD pathogenesis via phospholipids oxidation and MCP-1 induction.

Keywords: age-related macular degeneration • pathology: experimental • oxidation/oxidative or free radical damage