Selective Ganglion Cell Functional Loss in Rats with Experimental Glaucoma

Fortune, Brad; Bui, Bang V.; Morrison, John C.; Johnson, Elaine C.; Dong, Jing; Cepurna, William O.; Li, Jia; Barber, S.L.; Cioffi, George A.

doi:10.1167/iovs.03-1411

Cited by 133 publications

(127 citation statements)

References 31 publications

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“…In the experimental glaucoma, the ERG changes (drop in amplitudes by up to 50%) preceded changes in the nerve fibers layer [11]. This fact, as well as other findings, [12][13][14] made us employ the electrophysiological techniques (PERG) to determine the level and layer of changes in the different glaucoma groups.…”

Section: Discussionmentioning

confidence: 74%

High Tension Versus Normal Tension Glaucoma. A Comparison of Structural and Functional Examinations

Lešták¹,

Nutterova²,

Pitrová³

et al. 2011

J Clinic Experiment Ophthalmol

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Section: Discussionmentioning

confidence: 74%

High Tension Versus Normal Tension Glaucoma. A Comparison of Structural and Functional Examinations

Lešták¹,

Nutterova²,

Pitrová³

et al. 2011

J Clinic Experiment Ophthalmol

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“…Earlier studies in this model and more recent reports on the saline injection glaucoma model indicate that decrease in ERG oscillatory potentials is an early indicator of glaucomatous pathophysiology of the retina, even before there is any morphologic pathology of RGC or axon loss (Bayer 2001;Grozdanic 2003;Fortune 2004;Neufeld 2004). Changes in a and b waves have also been documented in this glaucoma model (Grozdanic 2003) which seem to be a direct response to elevated IOP because the changes reverse when IOP returns to normal levels (Grozdanic 2003) as also found in the present experiments.…”

Section: Discussionmentioning

confidence: 77%

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model

Danias

Shen

Kavalarakis

et al. 2006

Experimental Eye Research

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Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains.IOP was raised in one eye of Wistar(N=5) and Brown-Norway(B-N)(N=7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats(N=7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined.Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. A group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs from contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared with contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (>30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones.The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.

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“…We used a well-characterized experimental model of glaucoma, in which a single injection of hypertonic saline into the episcleral veins of rat eyes induced chronic elevation of IOP, optic-nerve degeneration, and selective RGC loss by apoptosis, the sum effects of which resemble human glaucoma (20)(21)(22). The beneficial effect of NGF on RGC survival was demonstrated to be due to inhibition of apoptosis, as shown by the reduction in TUNEL RGC immunostaining and the greater retinal Bcl-2/Bax ratio.…”

Section: Discussionmentioning

confidence: 99%

Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma

Lambìase¹,

Aloe

Centofanti

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

199

155

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Elevated intraocular pressure (IOP) in glaucoma causes loss of retinal ganglion cells (RGCs) and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. We evaluated the effects of NGF eye drops in a rat model of glaucoma. We also treated 3 patients with progressive visual field defects despite IOP control. Glaucoma was induced in rats through injection of hypertonic saline into the episcleral vein. Initially, 2 doses of NGF (100 and 200 g/mL) were tested on 24 rats, and the higher dose was found to be more effective. NGF ͉ optic nerve ͉ retina

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Selective Ganglion Cell Functional Loss in Rats with Experimental Glaucoma

Cited by 133 publications

References 31 publications

High Tension Versus Normal Tension Glaucoma. A Comparison of Structural and Functional Examinations

High Tension Versus Normal Tension Glaucoma. A Comparison of Structural and Functional Examinations

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model

Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma

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