Cytoprotective effect of thioredoxin against retinal photic injury in mice.
OBJECTIVE
To determine the protective role of thioredoxin (TRX), an endogenous redox (reduction and oxidation) regulator, against retinal photic injury in mice.


METHODS
Four-week-old BALB/c mice were exposed to white fluorescent light (8000 lux) for 2 hours. The number of both the photoreceptor cell nuclei and the TUNEL-positive photoreceptor cell nuclei were counted to determine the severity of damage. Expression of endogenous TRX was analyzed in the retinal samples by immunohistochemistry and Western blot. Recombinant (r)TRX or mutant rTRX, in which cysteines in the active site are replaced with serines, was injected intravitreously into BALB/c mice before light exposure. Oxidized and tyrosine-phosphorylated proteins were analyzed in retinal samples to examine the antioxidative effect of TRX. The number of photoreceptor cell nuclei and the DNA ladder in the retinal samples were analyzed.


RESULTS
A significant reduction was observed in the number of photoreceptor cells and induction of TUNEL-positive nuclei after light exposure. TRX expression was enhanced in both the neural retina and retinal pigment epithelium after light exposure. The amounts of oxidized and tyrosine-phosphorylated proteins decreased in the neural retinas of the rTRX-treated mice compared with the vehicle- or mutant rTRX-treated mice. The reduction of photoreceptor cells and formation of a DNA ladder were suppressed by rTRX pretreatment but not with mutant rTRX.


CONCLUSIONS
TRX is induced in the retinal tissue after light exposure. Intraocular injection of rTRX suppresses photo-oxidative stress. TRX intensification may be a useful therapeutic strategy to prevent retinal photic injury.
Tanito
Masaki
M
Department of Biological Responses, Institute for Virus Research, Kyoto University, Sakyo, Kyoto, Japan.
Masutani
Hiroshi
H
Nakamura
Hajime
H
Ohira
Akihiro
A
Yodoi
Junji
J
D000818:Animals; D015153:Blotting, Western; D019610:Cytoprotection / Q000187:drug effects; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007267:Injections; D008027:Light; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000494:pharmacology; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013879:Thioredoxins / Q000378:metabolism / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism; D014822:Vitreous Body
D011994:Recombinant Proteins; D014443:Tyrosine; D013879:Thioredoxins