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Jana Sellers, Stephanie L Foster, Micah A Chrenek, P Michael Iuvone, Jeffrey H Boatright; DMSO protects against light-induced retinal degeneration, yet increases tyrosine nitration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2351.
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Oxidative damage underlies many retinal degenerations. DMSO scavenges hydroxyl radicals and crosses the blood-brain barrier. We hypothesize that systemic DMSO treatment suppresses oxidative damage related to light-induced retinal degeneration (LIRD).
Balb/c mice were injected IP with vehicle (Dulbecco’s PBS) or vehicle containing DMSO (3.74 g/kg), dark adapted overnight, injected once again, and exposed to 4 h of bright, toxic (5,000 lux) or dim (50 lux) light. ERGs were measured to assess retina function three weeks after exposure to toxic light. Morphology was assessed by optical coherence tomography (OCT) and by microscopy on plastic sections of eyes. Retinas were homogenized in PBS with protease inhibitors. Assessment of protein oxidation was indirectly measured as accumulation of tyrosine nitration via nitrotyrosine ELISA.
In vehicle treated groups, bright light exposure suppressed a-wave amplitude by 89.3±3.3% and b-wave amplitude by 88.9±2% as compared to dim controls. In DMSO treated groups, bright light suppressed a- and b-wave amplitudes 9.6±8.4% and 7.1±1.3%. There was no significant difference between vehicle dim controls and the DMSO bright group. The DMSO bright and vehicle bright groups were significantly different (N=3; p<0.0001, 2-way ANOVA with Tukey post-hoc analysis). Bright light exposure of vehicle-treated mice caused loss of most outer nuclear layer nuclei and inner and outer segments. Conversely, retinal morphology of mice exposed to toxic light but treated with DMSO was indistinguishable from dim controls. DMSO treatment did not alter ERG amplitudes or retinal morphology in dim controls. Compared to the dim light exposed, vehicle treated group, bright light exposure of vehicle treated mice resulted in a 211.9±19.3% increase in tyrosine nitration, suggesting increased oxidation due to LIRD. Surprisingly, DMSO treatment increased nitrotyrosine signal 289±29.1% and 338.6±27.5% in mice exposed to dim or bright light, respectively.
DMSO is protective in mice undergoing LIRD. Within the bounds of assessment by nitrotyrosine ELISA, DMSO does not appear to be acting as an antioxidant. That DMSO treatment increased tyrosine nitration may indicate that it induces oxidative damage prior to bright light exposure and that this is preconditioning and hence protective. We continue to explore the mechanism of action underlying DMSO-induced retinal protection.
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