Sodium Iodate Produces a Strain-Dependent Retinal Oxidative Stress Response Measured In Vivo Using QUEST MRI.
Sodium Iodate Produces a Strain-Dependent Retinal Oxidative Stress Response Measured In Vivo Using QUEST MRI.
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DOI：
10.1167/iovs.17-21850
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发表时间：
2017-06-01
影响因子：
4.4
通讯作者：
Roberts R
中科院分区：
文献类型：
--
作者：
Berkowitz BA;Podolsky RH;Lenning J;Khetarpal N;Tran C;Wu JY;Berri AM;Dernay K;Shafie-Khorassani F;Roberts R
我们在碘酸钠(SI)-萎缩易感（C57BL/6 [B6]）和SI-萎缩抗性（129S6/SvEvTac [S6]）小鼠的视网膜层内鉴定了非侵入性生物标志物，以测量氧化应激的严重程度。在B6和S6小鼠全身注射SI 24小时后，我们测量了：(1)体外全视网膜超氧化物的产生，(2)体内过多自由基的产生，基于α-硫辛酸（ALA）给药前后动物在磁铁内的层特异性1/T1值（淬灭辅助MRI [QUEST MRI]），(3)视觉表现（光动力学跟踪）±抗氧化剂；对照小鼠也进行了类似的评估。体内视网膜层间距和厚度也被评估（光学相干断层扫描，MRI）。si处理的B6小鼠视网膜产生的超氧化物明显高于si处理的S6小鼠。与si处理的S6小鼠相比，ala注射si处理的B6小鼠体内更多视网膜层的1/T1降低。未注射和盐水注射si处理的B6小鼠具有相似的视网膜1/T1谱。值得注意的是，si处理的B6小鼠的内节段1/T1层对ALA有反应，而si处理的S6小鼠则无反应。在两种si处理的菌株中，抗氧化剂提高对比敏感性的程度相似；抗氧化剂对两组患者的视力均无影响。治疗后24小时，两组si处理组的视网膜厚度均正常。QUEST MRI独特地测量了同一受试者视网膜层内过量自由基产生的严重程度。确定氧化应激遗传脆弱性的潜在机制有望帮助理解视网膜变性的发病机制。
We identify noninvasive biomarkers that measure the severity of oxidative stress within retina layers in sodium iodate (SI)-atrophy vulnerable (C57BL/6 [B6]) and SI-atrophy resistant (129S6/SvEvTac [S6]) mice. At 24 hours after administering systemic SI to B6 and S6 mice we measured: (1) superoxide production in whole retina ex vivo, (2) excessive free radical production in vivo based on layer-specific 1/T1 values before and after α-lipoic acid (ALA) administration while the animal was inside the magnet (QUEnch-assiSTed MRI [QUEST MRI]), and (3) visual performance (optokinetic tracking) ± antioxidants; control mice were similarly assessed. Retinal layer spacing and thickness in vivo also were evaluated (optical coherence tomography, MRI). SI-treated B6 mice retina had a significantly higher superoxide production than SI-treated S6 mice. ALA-injected SI-treated B6 mice had reduced 1/T1 in more retinal layers in vivo than in SI-treated S6 mice. Uninjected and saline-injected SI-treated B6 mice had similar transretinal 1/T1 profiles. Notably, the inner segment layer 1/T1 of SI-treated B6 mice was responsive to ALA but was unresponsive in SI-treated S6 mice. In both SI-treated strains, antioxidants improved contrast sensitivity to similar extents; antioxidants did not change acuity in either group. Retinal thicknesses were normal in both SI-treated strains at 24 hours after treatment. QUEST MRI uniquely measured severity of excessive free radical production within retinal layers of the same subject. Identifying the mechanisms underlying genetic vulnerabilities to oxidative stress is expected to help in understanding the pathogenesis of retinal degeneration.