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K. M. Joos, A. Jones, C. Li, D. Calkins; Effect of Intermittent IOP Elevation Over 12 Weeks in the Rat Retinal Neurochemical Signature. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3280.
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Intraocular pressure (IOP) fluctuations may occur over time in patients with glaucoma, but how these fluctuations affect the disease is difficult to assess. This study examined the effect of intermittent elevations in IOP in the rat retina.
The IOP was transiently elevated by ligation of the globe for 1 hour daily over 12 weeks, usually about noon, in the topically anesthetized right eye of 13 Sprague-Dawley rats. Five IOP readings were averaged for each measurement. While under deep anesthesia, the animals were perfused transcardially with 3% formaldehyde, 0.1% glutaraldehyde (v/v) and 0.2% picric acid (v/v) for immunohistochemistry, or were killed with rapid removal of retina for RT-PCR with 18S as the housekeeping gene.
Over 12 weeks, the mean baseline IOP OD was 14.8 + 3.0 mm Hg, increased to 35.8 + 5.2 mm Hg with treatment initiation, remained at 34.1 + 4.0 mm Hg at the conclusion of the 1-hour treatment, and returned to 15.6 + 1.2 mm Hg 1 hour after treatment completion. The mean baseline control IOP OS was 15.3 + 3.8 mm Hg and was 15.7 + 3.3 mm Hg after OD treatment completion. The following antibodies showed changes in the treated eye as reported in chronic glaucoma models: Thy-1 decreased in retinal ganglion cells, pNF-H&M decreased in the inner retina, c-Jun increased in retinal ganglion cells, vimentin increased in the inner nuclear layer, and NFKB increased in the inner retina. The ceruloplasmin, gamma synuclein, and phospholipase A2 group IB RT-PCR primers demonstrated increased mRNA (1.5 - fold, 5.3 - fold, 23 - fold, respectively) in the retinas challenged with intermittent IOP elevations compared to the contralateral untreated eyes.
Changes in the retina in rats with intermittent IOP elevations demonstrate changes similar to those found in models of chronically elevated IOP, supporting the hypothesis that intermittent elevations in IOP may produce glaucomatous damage with compromise of axonal transport.
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