Gullstrand Lab, Ophthalmology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):248-52. doi: 10.1167/iovs.11-8504.
To determine the protection factor (PF) for glutaredoxin-1 (Grx1) with regard to UVR-induced cataract by comparison of in vivo ultraviolet radiation (UVR) lens toxicity between double knockout Grx1⁻/⁻ and Grx1⁺/⁺ mice.
Twenty Grx1⁺/⁺ mice and 20 Grx1⁻/⁻ mice were unilaterally exposed in vivo to UVR for 15 minutes. Groups of four animals each received 0.0, 2.1, 2.9, 3.6, and 4.1 kJ/m(2) UVR-300 nm. At 48 hours after UVR exposure, light-scattering in the exposed and contralateral nonexposed lenses was measured quantitatively. Macroscopic lens changes were documented with dark-field illumination photography.
UVR-300 nm induced subcapsular and cortical cataract in Grx1⁻/⁻ and Grx1⁺/⁺ mice. In both Grx1⁻/⁻ and Grx1⁺/⁺, the light-scattering intensified with increased in vivo exposure doses of UVR-300 nm. The intensity of forward light-scattering was higher in the lenses of Grx1⁻/⁻ mice than in the lenses of Grx1⁺/⁺ mice. The threshold dose for in vivo UVR-300 nm-induced cataract, expressed as MTD(2.3:16), was 3.8 in the Grx1⁺/⁺ group and 3.0 in the Grx1⁻/⁻ group, resulting in a PF of 1.3.
The PF is an objective relative measure of protective properties. The Grx1 gene is associated with an in vivo PF of 1.3. This result signifies that the presence of the gene allows a 1.3 times longer in vivo exposure to UVR, at equivalent irradiance, than the absence of the gene before early-onset, UVR-induced cataract occurs. This finding indicates the important role of the Grx1 gene in the oxidation defense system of the lens.
通过比较双敲除谷氧还蛋白 1(Grx1)⁻/⁻和 Grx1⁺/⁺小鼠体内紫外线(UVR)晶状体毒性,确定谷氧还蛋白 1 对 UVR 诱导白内障的防护因子(PF)。
将 20 只 Grx1⁺/⁺小鼠和 20 只 Grx1⁻/⁻小鼠单侧进行体内 UVR 照射 15 分钟。每组 4 只动物分别接受 0、2.1、2.9、3.6 和 4.1kJ/m² UVR-300nm 的照射。在 UVR 暴露后 48 小时,定量测量暴露和对侧非暴露晶状体的光散射。用暗场照明摄影术记录宏观晶状体变化。
UVR-300nm 诱导 Grx1⁻/⁻和 Grx1⁺/⁺小鼠产生皮质和后囊下白内障。在 Grx1⁻/⁻和 Grx1⁺/⁺中,随着体内 UVR-300nm 暴露剂量的增加,光散射强度增强。Grx1⁻/⁻小鼠晶状体的前向光散射强度高于 Grx1⁺/⁺小鼠晶状体。Grx1⁺/⁺组体内 UVR-300nm 诱导白内障的 MTD(2.3:16)阈值剂量为 3.8,Grx1⁻/⁻组为 3.0,PF 为 1.3。
PF 是防护性能的客观相对衡量标准。Grx1 基因与体内 PF 为 1.3 相关。该结果表明,在发生早发性 UVR 诱导白内障之前,该基因的存在使晶状体在相同辐照度下能够多进行 1.3 倍的体内 UVR 暴露。这一发现表明 Grx1 基因在晶状体氧化防御系统中发挥了重要作用。