Delayed Cataract Repair and Increased Lens Light Scattering in Glrx1 Knockout Mice Following Exposure to UVR-B

Abstract

Purpose:: To investigate cataract evolution and cataract repair following unilateral in vivo exposure to above threshold doses UVR-B in Glutaredoxin 1 (Glrx1) homozygous knockout mice (Glrx1 ^-/-) and genetically matched wild type mice (Glrx1^+/+).

Methods:: A total of 30 six weeks old homozygous Glrx1 knockout mice (Glrx1^-/-) and 30 age matched Glrx1 wild type mice (Glrx1^+/+) were unilaterally exposed in vivo to UVR-B for 15 minutes. The radiation output of the UVR- source had _MAX at 302.6 nm with 4.5 nm [FWHM]. The animals received 1.5/ 3/or 5 times threshold dose (MTD_2.3:16) UVR-B depending on dose group (n=10). 48 hours following UVR - B exposure Glrx1 knockout and Glrx1 wildtype mice were sacrificed. Experimentally induced cataract was quantified as lens light scattering in the exposed and the contralateral not exposed lenses with a light dissemination meter (LDM meter). Evolution of cataract morphology was documented using grid and dark field illumination photography.

Results:: Exposed lenses of Glrx1 knockout and wildtype mice developed anterior subcapsular cataract 48 hours after exposure to UVR-B. Light scattering in Glrx1^-/- lenses was increased in all dose groups (1.5 MTD/ 3 MTD/ 5 MTD) as compared to lenses with normal Glutaredoxin 1 function. With increasing UVR-B dose cataract in Glrx1^-/- mice extended radially further towards the lens equator 48 hours post-exposure than in wild type animals. Furthermore anterior subcapsular cataract in knockout mice was less demarcated from clear lens areas compared to (Glrx1^+/+) mice lenses.

Conclusions:: Glrx1^-/- knockout mice lenses are more susceptible to oxidative stress induced by UVR-B exposure than lenses with normal Glrx1 function. Furthermore the inactivation of Glrx1 delays lens epithelial cell repair.

Keywords: cataract • radiation damage: light/UV • oxidation/oxidative or free radical damage