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F. Mabuchi, M. Aihara, J.D. Lindsey, R.N. Weinreb; Mouse Optic Nerve Axon Loss Is Related to Magnitude and Duration of Laser-Induced Ocular Hypertension . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3333.
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Purpose: To assess the relationship between ocular hypertension and optic nerve damage in mice. Methods: Ocular hypertension was induced unilaterally by laser photocoagulation at the limbus of NIH Swiss black mice. Intraocular pressure (IOP) was measured at weekly intervals using the microneedle method. The optic nerves of 13 laser-treated and control eyes were processed conventionally for electron microscopy, and the identity of the micrographs was masked prior to analysis. For each nerve, the cross-sectional area was measured in low magnification micrographs, and axonal and glial numbers were counted in 20 sets of high magnification micrographs. Results: The duration of high IOP ranged from 2 to 12 weeks (6.2 ± 3.6 weeks, mean ± SD). The mean and maximum IOP in the treated eyes were 1.5 and 1.6 times higher than those in the control eyes respectively (P < 0.0001). The optic nerve cross-sectional area, mean axonal density, and total axonal number in the treated eyes were significantly less than in the control eyes (by 28.5 ± 23.4%, 57.8 ± 37.8%, and 63.1 ± 38.1%, respectively; P<0.005 for each). The decrease of optic nerve cross-sectional area and the positive integral of IOP and time were significantly correlated with total axonal 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: There is a positive relationship between the magnitude and duration of IOP increase and total axonal loss in the optic nerve of the laser-induced ocular hypertensive mouse.
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