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Optic Nerve Damage in Experimental Mouse Ocular Hypertension

¹From the Hamilton Glaucoma Center, the ²National Center for Microscopy and Imaging Research, and the ³Department of Neurosciences, University of California San Diego, La Jolla, California.

PURPOSE. To evaluate optic nerve damage in mice after laser-induced ocular hypertension.

METHODS. Ocular hypertension was induced unilaterally in 13 NIH Black Swiss mice by laser photocoagulation of the limbus. Over the following 12 weeks, intraocular pressure (IOP) was measured at regular intervals by the microneedle method. The optic nerves of these mice and of seven normal untreated mice were then processed conventionally for electron microscopy, and cross sections of the nerve 300 µm posterior to the globe were collected. Low- and high-magnification images were collected systematically and masked before analysis. For each nerve, cross-sectional area was measured in low-magnification micrographs, and axon and glia numbers were counted in high-magnification micrographs.

RESULTS. In normal untreated mice, the average number of axons was 59,597 ± 3,112 (mean ± SD). Variation among these measurements was 5.7% ± 3.9%. After laser treatment, the duration of high IOP ranged from 2 to 12 weeks (6.2 ± 3.6 weeks, mean ± SD). The mean IOP in the treated eyes was 1.3 times greater than the mean IOP in the control eyes (P = 0.0012). The maximum IOP in the treated eyes was 1.6 times greater than that observed in the control eyes (P < 0.0001). The optic nerve cross-sectional area, mean axon density, and total number of axons in the treated eyes were significantly less than in the control eyes (28.5% ± 23.4%, 57.8% ± 37.8%, and 63.1% ± 38.1%, respectively; P < 0.005 for each). The decrease in optic nerve cross-sectional area and the positive integral of elevated IOP and duration of IOP elevation correlated significantly with total axon loss (r² = 0.79, P < 0.0001 and r² = 0.36, P = 0.040, respectively). The number of astrocytes per cross section of optic nerve was significantly greater in the treated eyes than in the control eyes (P = 0.014).

CONCLUSIONS. Laser-induced ocular hypertension in mouse eyes can induce optic nerve axon loss that correlates with the magnitude and duration of elevated IOP.

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