Absence of glutaredoxin1 increases lens susceptibility to oxidative stress induced by UVR-B.
We investigated if the absence of glutaredoxin1, a critical protein thiol repair enzyme, increases lens susceptibility to oxidative stress caused by in vivo exposure to ultraviolet radiation type B (UVR-B). Glrx(-/-) mice and Glrx(+/+) mice were unilaterally exposed in vivo to UVR-B for 15 min. Groups of 12 animals each received 4.3, 8.7, and 14.5 kJ/m(2) respectively. 48 h post UVR-B exposure, the induced cataract was quantified as forward lens light scattering. Cataract morphology was documented with darkfield illumination photography. Glutathione (GSH/GSSG) content was analyzed in Glrx(-/-) and Glrx(+/+) lenses. UVR-B exposure induced anterior sub-capsular cataract (ASC) in Glrx(-/-) and Glrx(+/+) mice. In Glrx(-/-) lenses the opacities extended further towards the lens equator than in wild type animals (Glrx(+/+)). Lens light scattering in Glrx(-/-) mice was increased in all dose groups compared to lenses with normal glutaredoxin1 function. The difference was more pronounced with increasing exposure dose. Lens sensitivity for UVR-B induced damage was significantly higher in Glrx(-/-) lenses compared to Glrx(+/+) lenses. The Glrx gene provides a 44% increase of protection against close to threshold UVR-B induced oxidative stress compared to the absence of the Glrx gene. In conclusion, the absence of glutaredoxin1 increases lens susceptibility to UVR-B induced oxidative stress in the mouse.
Meyer
Linda M
LM
Herzog Carl Theodor Eye Clinic, Nymphenburgerstrasse 43, Munich, Germany. linda.meyer@ste.ki.se
Löfgren
Stefan
S
Ho
Ye-Shih
YS
Lou
Marjorie
M
Wegener
Alfred
A
Holz
Frank
F
Söderberg
Per
P
D000818:Animals; D002386:Cataract / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D054477:Glutaredoxins / Q000172:deficiency* / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D012542:Scattering, Radiation; D014466:Ultraviolet Rays / Q000009:adverse effects*
D054477:Glutaredoxins; D005978:Glutathione