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Erin C. Fulchiero, Ratna Prasad, Pengcheng Lu, Karen M. Joos; Oxidative Injury of Optic Nerve Head Blood Vessels with Moderate IOP Elevation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4951.
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Glaucoma with destruction of retinal ganglion cells is a leading cause of irreversible worldwide blindness. The earliest pathological changes in glaucoma are not well understood. However, peroxynitrite-mediated oxidative injury has been implicated in glaucomatous RGC death and in optic nerve vasculature. Peroxynitrite-mediated oxidative injury has been reported in human glaucoma. In the current study, we evaluate whether evidence of peroxynitrite-mediated oxidative injury is present within the eye following early IOP elevation.
All experiments adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and were approved by the IACUC at Vanderbilt University. IOP was transiently elevated for 1 hour with an adjustable lasso around the right topically anesthetized eye of Sprague-Dawley rats. IOP was measured before, immediately after, at the end of 1 hour treatment, and 1 hour after rest using TonoLab tonometry (Tiolat Oy (Helsinki, Finland)). Following fixation perfusion, sagittal sections were prepared for immunohistochemistry with antibody to nitrotyrosine (Cell Signaling Technology). Intensity of immunoreactivity was assessed semi-quantitatively using the MetaMorph® Microscopy Automation & Image Analysis Software. Non-perfused retinas also were analyzed by Western blot with nitrotyrosine antibody.
Mean baseline IOP of 19.6+1.4 mm Hg increased to 43.6+1.1 mm Hg (P<0.01) during 1-hour treatments and returned to 20.4+2.3 mm Hg (P=0.75) one hour after completion. The final IOP was not significantly different from the final control eye IOP of 20.4+0.9 mm Hg (P=0.75). There was increased nitrotyrosine staining density in the treated eye compared to the contralateral control eye in the pre-laminar optic nerve vessels (P=0.04). No significant increase of nitrotyrosine staining was evident in the trabecular meshwork (P=0.38), combined nerve fiber and retinal ganglion cell layers (P=0.74), or inner plexiform layer (P=0.74) following the early IOP elevation. Increased anit-nitrotyrosine staining was present in the treated eyes by Western blot analysis.
Transiently elevated intraocular pressures can be produced consistently for 1 hour in the rat. One hour of moderate elevation in intraocular pressure increased nitrotyrosine immunohistochemical staining within the pre-laminar optic nerve vessels in our rat model. This is consistent with changes seen in chronic human glaucoma tissue.
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