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K.M. Joos, M. Putatunda, S. Saadat, A. Jones, R. Robinson, D. Calkins; Effect of Six–Week Intermittent Intraocular Pressure Elevation on the Morphometry of the Rat Optic Nerve . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1250.
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Intraocular pressure (IOP) fluctuations may occur over time in patients with glaucoma, but how these fluctuations affect axonal populations in the optic nerve is difficult to assess. This study examined the effect of intermittent elevations in IOP on the morphometry of the rat optic nerve.
The IOP was transiently elevated by ligation of the globe for 1 hour daily over 6 weeks, usually about noon, in one topically anesthetized eye of 10 Sprague–Dawley rats. Five IOP readings were averaged at each time. The animals were perfused transcardially with 3% formaldehyde, 0.1% glutaraldehyde (v/v) and 0.2% picric acid (v/v). Optic nerve segments (3–4 mm length) proximal to the globes were prepared for histological sectioning. Cross–sectional areas of nerves and axonal counts were quantified from 1–2 µm semi–thin sections using an automated imaging algorithm.
The mean baseline IOP 15.1+ 0.6 mmHg increased to 35.9+0.8 mmHg during the 1–hour treatments and returned to 16.3+2.8 mmHg 1 hour after treatment completion. Cross–sectional optic nerve areas decreased in the treated eyes to 0.24 + 0.05 mm2 compared to areas in the control eyes of 0.27 + 0.02 mm2 (Wilcoxon Signed Rank Test, P=0.049). Axonal counts of 91,100+ 20,500 in the treated eyes were not significantly decreased compared to counts of 96,800+11,900 in the untreated eyes (P=0.3). Three pairs of nerves showed histological reduction of the inter–fascicular area in the treated eyes which averaged 0.024+0.09 mm2 compared to a mean inter–fascicular area of 0.057+0.01 mm2 in the contralateral optic nerves.
Changes in the optic nerve architecture may become evident in rats as early as 6 weeks following intermittent IOP elevation. Although there was not a significant reduction in the number of ganglion cell axons, histological changes included loss of total nerve cross–sectional area with a suggestion of changes occurring within the inter–fascicular region.
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