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Bruce A Berkowitz, Jacob Lenning, Nikita Khetarpal, Catherine Tran, Johnny Wu, Robin Roberts; Low Dose Sodium Iodate Produces a Strain-dependent Retinal Oxidative Stress Response. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5909.
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© ARVO (1962-2015); The Authors (2016-present)
To compare biomarkers of pathogenic retinal oxidative stress, and its functional consequences, in two common mouse strains treated with sodium iodate.
C57BL6/J (B6) and 129S6 (S6) mice were treated with 20 mg/kg IP sodium iodate ± antioxidant methylene blue (MB) or vehicle, and then dark adapted. The next day, dark adapted layer-specific free radical production in vivo, and retinal thickness, were measured from 1/T1 MRI data (PMID: 26670830). Other sodium iodate treated groups were also studied the next day for retinal superoxide levels ex vivo (Lucigenin), contrast sensitivity (CS, optokinetic tracking) ± MB+α-lipoic acid (dosed per PMID: 26670830), and optical coherence tomography (OCT).
Compared to vehicle injected mice, MB quenched (p < 0.05) supernormal 1/T1 in the outer nuclear layer (48-72% depth) of S6 mice, and in the retinal pigment epithelium/outer segment layer (88-100% depth) of B6 mice. In these responsive regions, outer retinal 1/T1 was 33% lower (p < 0.05) in treated S6 mice than in treated B6 mice; whole retinal superoxide production was 46% lower (p < 0.05) in treated S6 than in treated B6 mice. In treated B6 and S6 mice, CS was 24% and 16% subnormal, respectively; MB+α-lipoic acid treatment improved CS only in the B6 group. Retinal thicknesses (OCT, MRI) were normal in treated B6 and S6 mice.
Across biomarkers, low dose sodium iodate caused significantly less retinal oxidative stress in S6 than in B6 mice. Identifying strain-dependent oxidative stress responses will help in the study of the pathogenesis of retinal degeneration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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