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1 From the Departments of Ophthalmology and 2 Neurology, Mount Sinai School of Medicine, New York University, New York.
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 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 microscopy.
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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