Gosbell Andrew D, Stefanovic Nada, Scurr Lyndee L, Pete Josefa, Kola Ismail, Favilla Ian, de Haan Judy B
Ophthalmology Research Group, Monash University, Department of Surgery, Monash Medical Centre, Clayton, Victoria, Australia.
Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2613-22. doi: 10.1167/iovs.05-0962.
The role of the antioxidant enzyme glutathione peroxidase-1 (GPx1) in protecting the retina against photo-oxidative damage was investigated in GPx1-deficient and wild-type mice.
Albino GPx1-deficient and age-matched wild-type mice were examined. Baseline electroretinograms (ERGs) were recorded. Thereafter, mice were exposed to intense light for 12 hours. After a 24-hour recovery in darkness, post-light-insult ERGs were recorded and compared with baseline. Structural effects of light insult were evaluated by retinal histology. Antioxidant expression was investigated by quantitative reverse transcription-PCR (qRT-PCR).
Light insult significantly affected ERG responses, with reduced a- and b-wave amplitudes. Structurally, photoreceptor layers were predominantly affected. As expected, GPx1 expression was negligible in GPx1-deficient mice but was upregulated in wild-type mice in response to light insult. Similarly, hemeoxygenase-1 and thioredoxin-1 expression increased significantly in wild-type retinas after light exposure. Catalase, GPx isoforms (GPx2 to -4), peroxiredoxin-6, glutaredoxin-1, and thioredoxin-2 expression was unaffected by GPx1 deficiency and light insult, whereas significant increases in glutaredoxin-2 occurred in non-light-exposed (baseline) GPx1-deficient retinas. Compared with baseline wild-type retinas, lipid peroxidation (TBARS assay), an indicator of oxidative stress, was elevated in baseline GPx1-deficient retinas. Unexpectedly, the light insult induced diminution of retinal function, in terms of ERG amplitude, and structural damage was significantly greater in wild-type than in with GPx1-deficient retinas.
The data showing increased oxidative damage in baseline GPx-deficient retina give rise to the hypothesis that increased oxidative stress provides a "preconditioning" environment in which protective mechanisms paradoxically render GPx1-deficient retinas less vulnerable to light-induced oxidative damage. This study identified glutaredoxin-2 as a potential candidate.
在谷胱甘肽过氧化物酶-1（GPx1）缺陷型和野生型小鼠中研究抗氧化酶GPx1在保护视网膜免受光氧化损伤中的作用。
检查白化病GPx1缺陷型和年龄匹配的野生型小鼠。记录基线视网膜电图（ERG）。此后，将小鼠暴露于强光下12小时。在黑暗中恢复24小时后，记录光损伤后的ERG并与基线进行比较。通过视网膜组织学评估光损伤的结构效应。通过定量逆转录聚合酶链反应（qRT-PCR）研究抗氧化剂表达。
光损伤显著影响ERG反应，a波和b波振幅降低。在结构上，光感受器层受到的影响最为明显。正如预期的那样，GPx1在GPx1缺陷型小鼠中的表达可忽略不计，但在野生型小鼠中，其表达因光损伤而上调。同样，野生型视网膜在光照后血红素加氧酶-1和硫氧还蛋白-1的表达显著增加。过氧化氢酶、GPx同工型（GPx2至-4）、过氧化物还原酶-6、谷氧还蛋白-1和硫氧还蛋白-2的表达不受GPx1缺陷和光损伤的影响，而在未暴露于光（基线）的GPx1缺陷型视网膜中，谷氧还蛋白-2显著增加。与基线野生型视网膜相比，氧化应激指标脂质过氧化（硫代巴比妥酸反应物测定）在基线GPx1缺陷型视网膜中升高。出乎意料的是，就ERG振幅而言，光损伤诱导的视网膜功能减退和结构损伤在野生型小鼠中比在GPx1缺陷型视网膜中显著更大。
数据显示基线GPx缺陷型视网膜中的氧化损伤增加，由此产生一个假说，即氧化应激增加提供了一种 “预处理” 环境，在这种环境中，保护机制反而使GPx1缺陷型视网膜对光诱导的氧化损伤更不易感。本研究确定谷氧还蛋白-2为一个潜在候选物。
