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Preston E Girardot, Robin H Schmidt, Jana T Sellers, Jeffrey H Boatright; Retinal Degeneration is Time- and Intensity-Dependent in Heterozygous Carriers of the Tvrm4 Rhodopsin Mutation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):617.
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© ARVO (1962-2015); The Authors (2016-present)
Mice that are heterozygous for the autosomal dominant Tvrm4 mutation (henceforth referred to as Tvrm4/+ mice) are a model of Class B Rho mutation retinitis pigmentosa. The utility of this model is limited by the fact that the Tvrm4/+ phenotype is still poorly understood. Tvrm4/+ mice display a typical C57BL/6 phenotype when raised under standard 12:12 h maintenance lighting conditions, but undergo retinal degeneration following very brief exposure to intense light. We sought to clarify the relationship between duration and intensity of light exposure and the extent of degeneration exhibited by Tvrm4/+. We also wanted to determine whether the retinal degeneration we observed worsens over time.
Male and female Tvrm4/+ mice were exposed to varying intensities of LED light (12,000 to 70,000 lux) for 1 or 5 minutes, with or without 0.2% atropine eye drops. Before light exposure and at 7 and 21 days after light exposure, retinal and visual function, as determined by electroretinogram (ERG) and optokinetic tracking (OKT) response, were measured. After 21 days, mice were sacrificed and eyes were fixed in glutaraldehyde and embedded in plastic medium for histological sectioning. Plastic sections were stained with toluidine blue for assessment of retinal morphology.
Bright light exposure led to decreases in ERG a- and b-wave response, as well as decreases in visual acuity and contrast sensitivity. The degree of vision loss varied in proportion to both light intensity and duration of exposure, with a complete loss of a- and b-wave response in mice exposed to 70,000 lux for 5 minutes and a ~50% loss of response in mice exposed to 50,000 lux for 5 minutes. The visual deficits present in these mice at 1 week post-light exposure did not worsen over time. Morphometric analysis of retinal sections revealed loss of photoreceptor nuclei, thinning of the outer nuclear layer, and chromatin aggregation in light-exposed mice.
The Tvrm4/+ mouse loses retinal and visual function following bright light exposure, with concomitant changes in the morphology of the retina. These changes correlate with both duration and intensity of light exposure, but do not appear to worsen when mice are returned to normal room lighting conditions.
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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