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Iron-generated hydroxyl radicals kill retinal cells in vivo: effect of ferulic acid

Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China; Department of Ophthalmology, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China; Department of Ophthalmology, China Medical University Hospital, Taiwan, Republic of China hsiao-ming.chao{at}vghtpe.gov.tw

YH Chen

Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China; Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China

JH Liu

Department of Ophthalmology, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan, Republic of China

SM Lee

Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China; Department of Ophthalmology, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China

FL Lee

Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China; Department of Ophthalmology, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China

Y Chang

Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China; Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan, Republic of China

PH Yeh

Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China

WHT Pan

Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China

CW Chi

Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China

TY Liu

Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China

WY Lui

Department of Surgery, Veterans General Hospital, Taipei, Taiwan, Republic of China; Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China

LT Ho

Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China

CD Kuo

Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China

DE Lin

Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China; Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China

CC Chan

Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China; Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan, Republic of China

DM Yang

Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan, Republic of China; Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China

AMY Lin

Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China

FP Chao

Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China; Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China hsiao-ming.chao{at}vghtpe.gov.tw

Siderosis bulbi is vision threatening. An investigation into its mechanisms and management is crucial. Experimental siderosis was established by intravitreous administration of an iron particle (chronic) or FeSO₄ (acute). After siderosis, there was a significant dose-responsive reduction in eletroretinogram (a/b-wave) amplitude, and an increase in ^•OH level, greater when caused by 24 mM FeSO₄ than that by 8 mM FeSO₄. Furthermore, the FeSO₄-induced oxidative stress was significantly blunted by 100 µM ferulic acid (FA). Siderosis also resulted in an excessive glutamate release, increased [Ca⁺⁺]_i, and enhanced superoxide dismutase immunoreactivity. The latter finding was consistent with the Western blot result. Obvious disorganization including loss of photoreceptor outer segments and cholinergic amacrines together with a wide-spreading ferric distribution across the retina was present, which were related to the eletro-retinographic and pathologic dysfunctions. Furthermore, b-wave reduction and amacrine damage were respectively, significantly, dose-dependently, and clearly ameliorated by FA. Thus, siderosis stimulates oxidative stress, and possibly, subsequent excitotoxicity, and calcium influx, which explains why the retina is impaired electro-physiologically and pathologically. Importantly, FA protects iron toxicity perhaps by acting as a free radical scavenger. This provides an approach to the study and treatment of the iron-related disorders such as retained intraocular iron and Alzheimer disease.

Key Words: Ca++ • ferulic acid • glutamate • iron • •OH

Human & Experimental Toxicology, Vol. 27, No. 4, 327-339 (2008)
DOI: 10.1177/0960327108092294


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