Mathu, Virginia1; Burkhalter, Rebecca2; Thao, Mason2; Kragerud, Ben2; Kiland, Julie A2
Departments of 1Ophthalmology and Visual Sciences; 2Surgical Sciences, University of Wisconsin-Madison
Purpose: Optomotor response (OMR), a reflex used to assess visual function in animals, has not been well characterized in either the optic nerve crush (ONC) or the magnetic microbead (MMB) model of ocular hypertension, two common mouse models of optic neuropathy. Additionally, it has seldom been used to describe visual function in 5XFAD mice, a model of familial Alzheimer’s disease (AD) due to β-amyloid accumulation. Here we combine the 5XFAD model of AD with ONC or MMB injection and measure their effects on visual function using OMR testing.
Methods: At 9 mths of age, OMR ratios were measured in 5XFAD (n=97; male n=56, female n=41) and wt C57BL/6J littermates (n=79; male n=43, female n=36) mice (qOMR system, Phenosys). Subsets of mice had undergone ONC (5XFAD n=26, WT n=22), sham surgery (5XFAD n=24, WT n=18), magnetic microbead injection (3 intracameral injections over 6 mths; 5XFAD n=12, WT n=15) or saline injection (5XFAD n=17, WT n=11), with all interventions initiated at 3mo. Mice were exposed to rotating visual stimuli of the following spatial frequencies: 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, and 0.6 cycles per degree (cpd). Mice were exposed to the stimuli 4 times (over two testing days) and optomotor response ratios averaged from these testing sessions for each eye.
Results: OMRs ratios at 0.2cpd were statistically significantly reduced in ONC eyes compared to naïve control eyes (5XFAD p<0.0001, wt p<0.0001) and compared to sham surgery controls (5XFAD p<0.0001, wt p<0.0001). Responses were also diminished in ONC eyes compared to contralateral eyes in both the 5XFAD and WT animals (p<0.0001, p<0.0001 respectively), with statistically significant differences persisting through 0.35 cpd. MMB injection also reduced OMR ratios but this difference was only statistically significant in MMB-injected wt eyes compared to wt naïve eyes at 0.2 cpd (p=0.0212). No statistically significant differences in OMR ratios were detected between naïve wt and naive 5XFAD mice, or between male and female mice in any group at 9 mo.
Conclusions: Quantitative OMR testing represents a viable non-invasive method to quantify unilateral reduction in visual function in awake 5XFAD and WT mice following ONC or MMB injection.
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