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Thom W. Mittag, John Danias, Geralyn Pohorenec, Hong–Mei Yuan, Evren Burakgazi, Ruth Chalmers–Redman, Steven M. Podos, William G. Tatton; Retinal Damage after 3 to 4 Months of Elevated Intraocular Pressure in a Rat Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3451-3459.
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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)
methods. An approximate doubling of IOP was induced in one eye (G) of female
Wistar rats (150–180 g) by cautery of 3 episcleral/limbal veins. At
intervals over 3 to 4 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 3 to 4 months of elevated IOP, RGCs were
fluorescently labeled with Fluorogold (retrogradely from the superior
colliculus), or retinas were labeled by intravitreal injection of a
mitochondrial potential indicator dye and stained for apoptotic
nuclei with a DNA dye. Flatmounts of fixed, dye-labeled retinas were
examined by epifluorescence, confocal, or interference contrast
results. Elevated IOP was consistently maintained for up to 4 months in G eyes,
but ERG a- and b-waves showed a statistically significant decline, of
30% to 40% in amplitude, after 3 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 totaled 2% to 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 3 to 4 months of ∼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.
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