Iron-generated hydroxyl radicals kill retinal cells in vivo: effect of ferulic acid.
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 FeSO(4) (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 FeSO(4) than that by 8 mM FeSO(4). Furthermore, the FeSO(4)-induced oxidative stress was significantly blunted by 100 microM 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.
Chao
H M
HM
Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China. hsiao-ming.chao@vghtpe.gov.tw
Chen
Y H
YH
Liu
J H
JH
Lee
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Lee
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Chang
Y
Y
Yeh
P H
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Pan
W H T
WH
Chi
C W
CW
Liu
T Y
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Lui
W Y
WY
Ho
L T
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Kuo
C D
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Lin
D E
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Chan
C C
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Yang
D M
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Lin
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Chao
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D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D003373:Coumaric Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004596:Electroretinography / Q000187:drug effects; D005296:Ferrous Compounds / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D005971:Glutamates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism / Q000633:toxicity; D007267:Injections; D007501:Iron / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012806:Siderosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014822:Vitreous Body / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D003373:Coumaric Acids; D005296:Ferrous Compounds; D005971:Glutamates; D017665:Hydroxyl Radical; C020748:ferrous sulfate; C004999:ferulic acid; D007501:Iron; D013482:Superoxide Dismutase; D002118:Calcium