Morphometric Changes in the Rat Optic Nerve Following Short-term Intermittent Elevations in Intraocular Pressure

PURPOSE. Intraocular pressure (IOP) fluctuations may occur in patients with glaucoma, but how these fluctuations affect axonal populations in the optic nerve and other structures in the eye has been difficult to assess. This study developed a rat model to evaluate the effect of intermittent controlled elevations in IOP on the morphology of the rat optic nerve. METHODS. IOP was transiently elevated for 1 hour on each of 6 days a week over 6 weeks with an adjustable vascular loop around the right topically anesthetized eye of Sprague-Dawley rats. IOP was measured by pneumatonometer before, immediately after, and at the end of 1 hour of treatment with ligature. Globes and optic nerve segments were prepared for histology and morphometry. RESULTS. Mean baseline IOP of 14.9 +/- 1.8 mm Hg increased to 35.3 +/- 2.6 mm Hg (P < 0.001) during 1-hour treatments and returned to 15.0 +/- 2.2 mm Hg (P = 0.84) 1 hour after completion. The contralateral untreated eyes had a mean IOP of 14.2 +/- 1.9 mm Hg at baseline and 14.6 +/- 1.9 mm Hg at the end of treatment. Nerve fiber layer thinning (22%-25%) corresponded with a decrease (7%-10%) in soma number in the ganglion cell layer. Optic nerves displayed axonal degeneration with a modest axon loss of 6% and increased expression of glial acidic fibrillary protein in astrocytes. CONCLUSIONS. Controlled daily 1-hour IOP elevations can be performed with an adjustable vascular loop in rats. After only 6 weeks, intermittent elevations in IOP produce changes in optic nerve consistent with early degeneration reported in chronic models of glaucoma. (Invest Ophthalmol Vis Sci. 2010;51:6431-6440) DOI:10.1167/iovs.10-5212