Modeling of risk factors for the degeneration of retinal ganglion cells following ischemia/reperfusion in rats: effects of age, caloric restriction, diabetes, pigmentation, and glaucoma

Kawai, Shinichiro; Vora, Smita C.; Das, Subhadeep; Gachie, E.; Becker, Bernard; Neufeld, Arthur H.

doi:10.1096/fj.00-0666fje

Cited by 70 publications

(50 citation statements)

References 48 publications

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“…This result may be due to the advanced age (~ 18 months old at the time of sacrifice) as well as the gender and strain difference. A sex difference has been reported for the susceptibility of DBA mice (John 1998) to glaucoma and the age-related decline of RGC numbers has been documented for several rat and mouse strains (Kawai 2001;Danias 2003). Our results on the total RGC counts in normal B-N rat eyes are less than those determined by Cepurna et al (Cepurna 1988) who used the same strain and estimated the total RGC count of B-N rats to be ~100K by a sampling count of the optic nerve axons.…”

Section: Discussionmentioning

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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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: 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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“…234 Calorie restriction has been shown to facilitate retinal ganglion cell recovery in acute intraocular pressure challenge and ischemia-reperfusion models. 235 Glucose restriction has been shown to activate AMPK, which then activated the gene for the NAD synthetic enzyme, Nampt. 236 This highlighted an important convergence between AMPK and SIRT1 in mitochondrial biogenesis (Figure 2).…”

Section: Regulation Of Mitochondrial Biogenesis As a Therapeutic Targetmentioning

confidence: 99%

Mitochondrial disorders and the eye

Bergen

Chakrabarti

O'Neill

et al. 2011

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Abstract:The clinical significance of disturbed mitochondrial function in the eye has emerged since mitochondrial DNA (mtDNA) mutation was described in Leber's hereditary optic neuropathy. The spectrum of mitochondrial dysfunction has become apparent through increased understanding of the contribution of nuclear and somatic mtDNA mutations to mitochondrial dynamics and function. Common ophthalmic manifestations of mitochondrial dysfunction include optic atrophy, pigmentary retinopathy, and ophthalmoplegia. The majority of patients with ocular manifestations of mitochondrial disease also have variable central and peripheral nervous system involvement. Mitochondrial dysfunction has recently been associated with agerelated retinal disease including macular degeneration and glaucoma. Therefore, therapeutic targets directed at promoting mitochondrial biogenesis and function offer a potential to both preserve retinal function and attenuate neurodegenerative processes.

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“…The diet restriction has a neuroprotective effect and thus, leads to lesser damage to RGCs. As seen in the case of glaucoma, pre-existing diabetes is a reason for greater harm to RGCs (Kawai et al, 2001). Genetic background is one of the principal determinants of susceptibility to retinal neovascularisation and breakdown of blood retinal barrier.…”

Section: Susceptibility To Retinal Ischemiamentioning

confidence: 99%