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Preston Girardot, Micah A Chrenek, Priscila Cunha, Jana Sellers, J M Nickerson, Jeffrey H Boatright; Brief-Period Light Preconditioning: Effects of Intensity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):429.
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Preconditioning refers to exposure to stressful but nontoxic stimuli that protects against subsequent toxic insult. We previously reported that exposing mice to bright light for a brief period protects against light-induced retinal degeneration. Here we investigated whether there is a dose-response relationship between the intensity of light used in preconditioning and the amount of resulting protection.
129S2/SvPasCrl mice were obtained from Charles River and kept in a 12:12 hour light: dark cycle. Mice were dark adapted one day prior to light preconditioning. The day of preconditioning, mice were treated with 1% atropine eye drops with a 30 min dilation period, followed by a 4 h exposure to no preconditioning (approximately 50 lux), 1000, 3000, and 5000 lux light. Twenty four hours later, mice either exposed to dim light (50 lux) or bright toxic light (50,000 lux) for 4 h. At least one week later, retinal function was assessed by scotopic electroretinography (ERG) and visual acuity was assessed by optokinetic tracking system (OKT).
In mice that had no preconditioning, toxic light exposure diminished mean ERG amplitudes to 27±3.7% (a-wave) and 23±3.2% (b-wave) of dim controls (p<0.0001). Preconditioning using 3000 and 5000 lux light preserved ERG a-wave amplitudes (p<0.0005) and preconditioning at all intensities preserved ERG b-wave amplitudes (p<0.0001). The amount of preservation increased with increasing light intensity (r2=0.96 and 0.97 for a- and b-wave amplitudes, respectively). Preconditioning using 3000 and 5000 lux light did not significantly alter ERG responses in mice not exposed to toxic light. Exposure to toxic light significantly decreased visual acuity from 0.4981±0.0044 to 0.2675±0.037 cycles/degree (n=8, p<0.0001). Visual acuity of mice exposed to toxic light was significantly greater if with preconditioning (p<0.003, no preconditioning versus any intensity) and was statistically indistinguishable in mice not exposed to toxic light.
These data suggest that protective light preconditioning can be as brief as a single 4 hour exposure and can be optimized by altering intensity, all without diminishing retinal function. This dosing approach provides an alternative to long-established preconditioning approaches that require several days of cyclic light exposure and may be confounded by inherent damage to photoreceptors.
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