Short Term Mild Ocular Hypertension in Mouse Induces Optic Nerve Fiber Change and Optokinetic Visual Deficit

Abstract

Methods: : Unilateral OHT was induced in 5 male young adult pigmented SV-129 mice by intracameral injection of latex microspheres. Vehicle-injected mice were used as controls (n=6). Intraocular pressure (IOP) was measured using Tonolab at 4 day intervals. Random and systematic photos of optic nerve specimens using a 4 MP Digital Camera under electron microscopy at 12000 magnification were obtained. By random selection, fibers were counted (1% of fibers) and axon size measured with a 5.35µm x 5.35µm Nucleator module counting frame (Streoinvestigator). Mean axon diameter was calculated for OHT (n=3046) and control (n=3353) groups. The optokinetic head response to a rotating whole field stimulus consisting of alternating black and white strips (spatial frequencies: 0.033 and 0.066 (cycle/degree)) was tested. Stimulus speed ranged from 1°/sec to 60°/sec, clockwise and counter-clockwise. The frequency of extinction (FE; cycles/sec), defined as the maximum speed at which an optokinetic head response could be observed, was recorded. OHT group was compared with controls using a two-tailed t test.

Results: : Mean IOP was increased for 6 weeks in the OHT group compared to controls (24.1mmHg ± 0.5 (mean±SD) vs. 14.5mmHg±0.4). The mean nerve fibre number in OHT was not different from controls (66988±10885 vs. 61427±4745; P>0.05). The mean axon diameter in the OHT group ranged from 0.64µm to 0.86µm, while the mean axon diameter in the controls ranged from 0.72µm to 0.81µm. Mean of the mean axon diameters in the OHT group did not differ from that of the controls (0.75µm ± 0.10 vs. 0.76µm±0.03; P = 0.9). However, for two of the five OHT cases, the mean axon diameters were below the 95% lower confidence limits of the six controls. For one OHT case, the mean axon diameter was above the 95% upper confidence limits of the six controls. Optokinetic response was significantly lower in OHT compared to controls (FE at 0.066cycle/degree stimulus: 0.9±1.8 cycle/sec vs. 5.9±1.0 cycle/sec; P<0.05).

Keywords: microscopy: electron microscopy • intraocular pressure • eye movements