Sodium Iodate Produces a Strain-Dependent Retinal Oxidative Stress Response Measured In Vivo Using QUEST MRI

被引:41
作者
Berkowitz, Bruce A. [1 ,2 ]
Podolsky, Robert H. [3 ]
Lenning, Jacob [1 ]
Khetarpal, Nikita [1 ]
Tran, Catherine [1 ]
Wu, Johnny Y. [1 ]
Berri, Ali M. [1 ]
Dernay, Kristin [1 ]
Shafie-Khorassani, Fatema [3 ]
Roberts, Robin [1 ]
机构
[1] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA
[2] Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI 48201 USA
[3] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA
关键词
QUEST MRI; free radicals; reactive oxygen species; strain; sodium iodate; CONE CELL-DEATH; LIGHT-INDUCED DEGENERATION; FREE-RADICAL PRODUCTION; MOUSE MODEL; DIABETIC-RETINOPATHY; RECEPTOR EXPRESSION; DAMAGE; MICE; ANTIOXIDANTS; PERFORMANCE;
D O I
10.1167/iovs.17-21850
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. 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. METHODS. 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 a- lipoic acid (ALA) administration while the animal was inside the magnet (QUEnch- assiSTed MRI [QUEST MRI]), and (3) visual performance (optokinetic tracking) 6 antioxidants +/- control mice were similarly assessed. Retinal layer spacing and thickness in vivo also were evaluated (optical coherence tomography, MRI). RESULTS. SI-treated B6 mice retina had a significantly higher superoxide production than SItreated 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. CONCLUSIONS. 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.
引用
收藏
页码:3286 / 3293
页数:8
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