Induction of heme oxygenase 1 in the retina by intense visible light: suppression by the antioxidant dimethylthiourea.
The effect of intense visible light (light damage) on the expression of heme oxygenase 1 (HO-1), a protein induced by oxidative stress, was investigated in the rat retina. A sensitive reverse transcription-PCR assay demonstrated the expression of mRNA for HO-1 as well as HO-2, the noninducible HO form, in the normal retina. As analyzed by Northern blotting, however, HO-1 mRNA was barely detectable under normal circumstances. After exposure to intense visible light, retinas had markedly higher HO-1 mRNA levels than unexposed controls, with increases up to 52- and 98-fold at 12 and 24 hr of exposure, respectively. Intense light exposure also resulted in an increase in HO-1 protein. In contrast, no appreciable change in HO-2 mRNA or protein was observed. The increase in HO-1 message was more pronounced in rats previously reared in the dark than in those reared in a weak cyclic-light environment. A marked decrease from the high level of HO-1 mRNA induced by light insult was observed when the animals were allowed to recover in the dark for 24 hr after light exposure. Most important, treatment of animals with 1,3-dimethylthiourea, a synthetic antioxidant, prior to light exposure effectively blocked the increase in HO-1 mRNA. Thus, HO-1 is a sensitive marker for assessing light-induced insult in the retina. Since increased expression of HO-1 is thought to be a cellular defense against oxidative damage, its expression may play an important role in protecting the retina against light damage.
Kutty
R K
RK
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Kutty
G
G
Wiggert
B
B
Chader
G J
GJ
Darrow
R M
RM
Organisciak
D T
DT
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D004790:Enzyme Induction / Q000528:radiation effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D008027:Light; D008297:Male; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D017931:DNA Primers; D012333:RNA, Messenger; C038983:1,3-dimethylthiourea; D006419:Heme Oxygenase (Decyclizing); D013890:Thiourea