Electroretinographic Abnormalities in a Rat Glaucoma Model with Chronic Elevated Intraocular Pressure

Bayer, Andreas; Danias, John; Brodie, Scott E.; Maag, Klaus-Peter; Chen, B; Shen, Fran; Podos, Steven M.; Mittag, Thomas W.

doi:10.1006/exer.2001.1004

Cited by 73 publications

(47 citation statements)

References 31 publications

(30 reference statements)

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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: 67%

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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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Section: Discussionmentioning

confidence: 67%

“…For the B-N rats, baseline and pre-sacrifice scotopic flash ERGs were recorded using goldwire plastic hard contact lens electrodes as previously described (Bayer 2001). ERGs were recorded from both eyes after animals had been dark adapted overnight.…”

Section: Methodsmentioning

confidence: 99%

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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“…Elevated IOP is considered a primary risk factor for the initiation and progression of glaucomatous optic neuropathy. [1][2][3][4][5][6][7] It is recognized that mammalian RGCs whose axons are cut or severely injured along the nerve or tract generally do not survive, that elevated IOP blocks retrograde axonal transport, and that the interruption of the supply of an unknown factor to RGCs may contribute to cell loss in glaucoma. [8][9][10] Studies carried out over decades have therefore used the following variety of possible glaucoma models induced by different mechanisms in rodents: Crush/axotomy model, Ischemia/reperfusion model, Excitotoxic damage, Induction of elevated IOP(vein occlusion, laser, S-antigen) and spontaneous elevat- Time (After surgery) FG labeled cell count / Unit area ed IOP.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] Studies carried out over decades have therefore used the following variety of possible glaucoma models induced by different mechanisms in rodents: Crush/axotomy model, Ischemia/reperfusion model, Excitotoxic damage, Induction of elevated IOP(vein occlusion, laser, S-antigen) and spontaneous elevat- Time (After surgery) FG labeled cell count / Unit area ed IOP. [1][2][3][4][5][6][7][8][9][10][11][12][13] The crush/axotomy model can quantify the primary damage and demonstrate a secondary degeneration. The crush model mimics very closely the damage which occurs in traumatic optic neuropathy (TON).…”

Section: Discussionmentioning

confidence: 99%

“…Elevated intraocular pressure (IOP) is considered a primary risk factor for the initiation and progression of glaucomatous optic neuropathy and preferentially kills RGCs without causing ancillary injury to the retina and ocular structures. [1][2][3][4][5][6][7] Various animal models have been proposed including optic nerve transsection and crush, ischemia and reperfusion, excitotoxic damage, episcleral vein occlusion or hypertonic saline injection or trabecular meshwork transphotocoagulation, and spontaneous intraocular pressure elevations. [1][2][3][4][5][6][7][8][9][10][11][12][13] The cautery of two or three episcleral veins is the most commonly used procedure.…”

Section: Introductionmentioning

confidence: 99%

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Ganglion Cell Death in Rat Retina by Persistent Intraocular Pressure Elevation

Kim¹,

Kim²,

Ahn³

et al. 2004

Korean J Ophthalmol

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Glaucoma is characterized by loss of retinal ganglion cells(RGCs) and their axons.Retrograde axoplasmic transport blockade and excitotoxicity were proposed to be a major cause of RGC apoptosis. We conducted this study to characterize the episcleral vessel cauterization glaucoma model in the rat with respect to decreased retrograde axoplasmic flow and subsequent apoptotic RGC death. After episcleral vessels were cauterized in Sprague-Dawley rats, Fluorogold was injected into their superior colliculi by stereotactic method. Retrograde axoplasmic flow and TUNEL-stained apoptotic dead cells were observed microscopically. Elevated intraocular pressure was maintained for up to 6 weeks during follow-up. Retrograde axoplasmic flow to the rat retina was significantly decreased. Apoptotic RGC was selectively TUNELstained in the retina, especially at the ganglion cell layers. We concluded that elevated intraocular pressure caused apoptotic RGC death through retrograde axoplasmic flow blockage. Further studies will elucidate the neuroprotection strategies in glaucoma patients.

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Alterations in photoreceptor‐bipolar cell signaling following ischemia/reperfusion in the rat retina

Sun

Bui

Kalloniatis

2007

J of Comparative Neurology

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Studies of retinal ischemia/reperfusion indicate a disparity between the anatomical and functional results; while a large number of rod bipolar cells remain postischemia, there is a significant reduction in the amplitude of the scotopic b-wave of the electroretinogram (ERG). We investigated the alterations in photoreceptor-bipolar cell signaling following ischemia/reperfusion and suggest a mechanism for the decrease in b-wave amplitude. A cation channel probe (agmatine, 1-amino-4-guanidobutane, AGB) was used to assess cellular ion channel activity in neurochemically identified cells secondary to endogenous glutamate release or pharmacological manipulations. By applying the "neurochemical truth point" principle (Sun et al. [2007a] J Comp Neurol, this issue), we have been able to confirm the loss of specific subpopulations of neurons. ERG was used to assess gross retinal function, with parameters of the ERG model providing insight into changes in the phototransduction cascade and sensitivity of postreceptoral glutamate receptors. Following ischemia/reperfusion, rod bipolar cells maintained 2-amino-4-phosphonobutyric acid-responsive metabotropic glutamate receptors and displayed no change in sensitivity to flashes of light as assessed by ERG. Therefore, the loss in b-wave amplitude is likely due to alterations in photoreceptoral glutamate release detected as a change in postsynaptic AGB permeation into rod bipolar cells. Bipolar cell to amacrine cell signaling was also altered. The robust AGB entry into cholinergic amacrine cells was virtually absent in retinas that had undergone ischemia/reperfusion but remained in the AII amacrine cells. Such results suggest a loss of glutamate receptors and/or a change in receptor subunit expression in subpopulations of inner retinal neurons. Although many cells retain their characteristic neurochemical labeling following ischemia/reperfusion, caution should be used when assuming cells participate in functional retinal circuits based solely on the persistence of neurochemical labeling.

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Electroretinographic Abnormalities in a Rat Glaucoma Model with Chronic Elevated Intraocular Pressure

Cited by 73 publications

References 31 publications

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

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

Ganglion Cell Death in Rat Retina by Persistent Intraocular Pressure Elevation

Alterations in photoreceptor‐bipolar cell signaling following ischemia/reperfusion in the rat retina

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