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Kin-Sang Cho, Jiaxin Xiao, Muhammed Yasin Adil, Tor Utheim, Dong Feng Chen; Contrast sensitivity threshold correlates to the progressive degeneration of photoreceptors in a mouse model of retinitis pigmentosa.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4540.
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© ARVO (1962-2015); The Authors (2016-present)
Rhodopsin knockout mouse (Rho-/-) is a commonly used model for studying the mechanism and treatment strategies of photoreceptor degeneration in retinitis pigmentosa. The optomotor responses (OMR) and visual perception during disease progression in Rho-/- mice is less clear. Thus, we will investigate the OMR and its correlation to the progressive loss of photoreceptors and retinal function in Rho-/- mice.
The survival of photoreceptors, retinal function and visual performance of wild type (WT) and Rho-/- mice (n=8/group) were tracked non-invasively in live animals biweekly starting from 6 weeks old up to 12 weeks old. Retinal structure was imaged by spectrum domain-optic coherence tomography (SD-OCT; Bioptigen) and the outer nuclear layer (ONL) thickness was quantified by Image J software. The b-wave amplitude of ERG response with light and dark-adapted conditions was measured by ColorDome (Diagnosys). The the contrast sensitivity (CS) and visual acuity (VA) thresholds of OMR was examined. All experiments were performed in a masked fashion. Statistical analysis was performed using SPSS (v23.0).
In WT mice, the ONL thickness, ERG responses and OMR remained constant up to 12 weeks old. As expected, 6 weeks old Rho-/- mice showed a significant thinner ONL comparing to age-matched WT mice (Mann-Whitney U test, P<0.05). Rho-/- mice displayed a progressive decrease of ONL thickness and b-wave amplitude (One-way AVOVA with Games Howell post hoc test, P<0.05) from 6 – 12 weeks. Correlating with progressive photoreceptor loss, we observed significant and progressive declines of CS threshold in 6 to 12 weeks old Rho-/- mice (One-way AVOVA with Games Howell post hoc test, P<0.05). Nevertheless, the VA threshold was rather constant until an abrupt drop at 12 weeks old. The CS threshold in Rho-/- mice displayed a stronger association with the reduction of ONL thickness (r=0.94) and b-wave amplitude ((r=0.8) of ERG (P<0.05 for all).
Contrast sensitivity has a strong correlation to the ONL thickness and the retinal function of Rho-/- mice. It suggests that OMR could be a non-invasive approach to evaluate the progression of photoreceptor degeneration in Rho-/- mice or in other animal models of photoreceptor 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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