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Abstract #15859 Published in IGR 2-3
Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model
Mittag TW; Danias J; Pohorenec G; Yuan HM; Burakgazi E; Chalmers-Redman R; Podos SM; Tatton WGInvestigative Ophthalmology and Visual Science 2000; 41: 3451-3459
PURPOSE: To characterize a long-term elevated intraocular pressure (IOP) glaucoma model in the rat with respect to electroretinographic (ERG) changes and the pattern and mechanism of retinal ganglion cell (RGC) death. METHODS; An approximate doubling of IOP was induced in one eye (G) of female Wistar rats (150-180 g) by cautery of three episcleral/limbal veins. At intervals over three to four months, measurements of IOP and ERG changes (contact-lens electrode) were made in both the G and contralateral normal (N) eyes. At the end of three to four months of elevated IOP, RGCs were fluorescently labelled with Fluorogold (retrogradely from the superior colliculus), or retinas were labelled by intravitreal injection of a mitochondrial potential indicator dye and stained for apoptotic nuclei with a DNA dye. Flatmounts of fixed, dye-labelled retinas were examined by epifluorescence, confocal, or interference contrast microscopy. RESULTS: Elevated IOP was consistently maintained for up to four months in G eyes, but ERG a- and b-waves showed a statistically significant decline, of 30% to 40% in amplitude, after three months. Loss of RGCs in G retinas was primarily focal with no statistically significant loss demonstrable outside of the focal areas when assessed by an area sampling method for counting RGCs, which totalled 2-3% of the entire retinal area. Mitochondrial membrane potential of cells in the RGC layer was reduced by 17.5% (p < 0.05) in regions surrounding areas of focal loss compared with comparable locations in control N eyes. After 3.5 months' elevated IOP, the G retinas showed cell nuclei at various stages of apoptosis, from initial DNA condensation to fragmentation. CONCLUSIONS: The three-vein episcleral/limbal vein occlusion model for inducing glaucomatous pathology in the rat eye gives a consistent long-term elevation of IOP. After three to four months of approximately 100% increased IOP, the ERG responses begin to decline, there is a variable focal loss of RGCs, and some of the remaining RGCs show characteristics of stress and apoptosis. These changes seem consistent with retinal damage in human glaucoma (focal field defects), and this rat model appears to mimic some features of primary open-angle glaucoma.
Dr. T.W. Mittag, Departments of Ophthalmology and Neurology, Mount Sinai School of Medicine, New York University, New York, NY 10029-6574, USA. thomas.mittag@mssm.edu
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)