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K. M. Joos, R. Sappington, R. Prasad, D. Calkins; Rat Retinal and Optic Nerve Changes with Daily 1-Hour Intraocular Pressure Elevation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3688.
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It is accepted that patients with glaucoma may have intraocular pressure (IOP) fluctuations over time. How these fluctuations may affect the disease is difficult to assess. This study examined the effect of daily IOP elevations in the the rat retina and optic nerve.
The IOP was transiently elevated with a silicone lasso around the globe for 1 hour daily over 12 weeks, in the topically anesthetized right eye of 10 Sprague-Dawley rats. Five IOP readings were averaged for each measurement. While under deep anesthesia, the animals were perfused transcardially. Myelinated optic nerves were separated from the globes. The globes were embedded in paraffin and sections were treated with glutamine synthetase antibody. Optic nerves were fixed overnight and embedded in Epon. Semi-thin cross-sections were stained with toluidine blue to visualize degenerating axonal profiles. We constructed full-nerve montages at 100 x using an automated algorithm. Degenerating axons were identifed by increased density and unwrapping of myelin sheaths, and counted by a masked observer.
The mean baseline IOP OD was 14.8 + 3.0 mm Hg and increased to 35.8 + 5.2 mm Hg with treatment initiation. IOP remained at 34.1 + 4.0 mm Hg at the conclusion of the 1-hour treatment, and returned to 15.6 + 1.2 mmHg 1 hour after treatment completion. Increased glutamine synthetase was observed in 80% of the treated eyes compared to the contralateral untreated retinas. A 2.8-fold increase in degenerating axons was observed in the treated eyes compared to the contralateral untreated eyes (P < 0.001).
Changes in the rat after only 12 weeks of daily 1-hour moderate IOP elevation demonstrated upregulation of glutamine synthetase consistent with observations in chronic glaucoma animal models. Additionally, intermittent IOP elevation caused a significant increase in the number of degenerating axons. This supports the hypothesis that intermittent elevations in IOP may compromise axonal integrity and function.
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