Dextromethorphan Protects Retina Against Ischemic Injury In Vivo

Yoon, Young Hee; Marmor, Michael F.

doi:10.1001/archopht.1989.01070010419037

Cited by 102 publications

(43 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Olney [2] advanced the concept of 'excitotoxicity' on the basis of the hypothesis that excessively released excitatory amino acids such as glutamate and aspartate overstimulate their receptors and lead to neural cell death. In the retina, it has been reported that extracellular glutamate increases after ischemia [3,4] and that the antagonists for the N-methyl-D-aspartate receptor suppress abnormal changes in the ischemic retina [5][6][7]. In addition to excitotoxicity, the formation of large amounts of oxygen-derived free radicals after ischemia and reoxygenation has been proposed to play an important role in neuronal injury [8,9].…”

Section: Introductionsupporting

confidence: 40%

Involvement of Oxygen Free Radicals in Experimental Retinal Ischemia and the Selective Vulnerability of Retinal Damage

Kuriyama

Waki

Nakagawa³

et al. 2001

Ophthalmic Res

View full text Add to dashboard Cite

Protective effects of CV-3611, a free radical scavenger, on retinal ischemic injury in the rat and on glutamate-induced cytotoxicity in a cell line were evaluated. Transient retinal ischemia was induced by raising intraocular pressure of rats to 110 mm Hg for 45 min, and the electroretinogram (ERG) was measured to evaluate retinal function. No ERG could be recorded immediately after reperfusion, and thereafter the ERG gradually recovered. Recovery of the a-wave latency and the amplitudes of the a and b waves in the CV-3611-treated (10 mg/kg, p.o.) group were significantly better than those in the control group up to 24 h after reperfusion. In both the control and CV-3611 group, the b wave showed better recovery than the a wave up to 6 h after reperfusion, while the relationship was reversed after 24-hour reperfusion. Glutamate (10 mM)-induced cytotoxicity in the N18-RE-105 cell, a neural retina-neuroblastoma hybridoma, was quantified by measuring lactate dehydrogenase. Three and 10 µM of CV-3611 significantly attenuated the glutamate-induced cytotoxicity in N18-RE-105 cells. Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity. These results suggest that oxygen free radicals play an important role in the early phase of retinal ischemic injury. Moreover, differential recovery processes of the a and b waves after ischemia suggest that the selective vulnerability of the retina to ischemia could change functionally during the period of reperfusion.

show abstract

Section: Introductionsupporting

confidence: 40%

Involvement of Oxygen Free Radicals in Experimental Retinal Ischemia and the Selective Vulnerability of Retinal Damage

Kuriyama

Waki

Nakagawa³

et al. 2001

Ophthalmic Res

View full text Add to dashboard Cite

show abstract

“…In support of the glutamate toxicity hypothesis is the report that blockage of synaptic transmission and antagonists of specific postsynaptic glutamate receptors, especially the NMDA receptors, are neuroprotective [9,14,15,17,18,[21][22][23]. For example, NMDA receptor antagonists have been reported to protect against hypoxicischemic damage of brain and retinal neurons in animal models.…”

Section: Discussionsupporting

confidence: 38%

“…Retinal ischemia was induced by increasing IOP to 140 mm Hg for 60 min as described by Yoon and Marmor [18]. The anterior chamber of one eye was cannulated with a 20-gauge hypodermic needle connected to a silicone elastomer tube, and the IOP was increased by raising the height of a balanced saline solution reservoir.…”

Section: Retinal Ischemiasupporting

confidence: 42%

Protective Effect of Docosahexaenoic Acid against Retinal Ischemic Injury: An Electroretinographic Study

Miyauchi

Mizota²,

Nishikawa³

2001

Ophthalmic Res

View full text Add to dashboard Cite

Purpose: To determine whether docosahexaenoic acid (DHA) can reduce the retinal damage induced by transient retinal ischemia. Methods: Retinal ischemia was induced by increasing intraocular pressure (IOP). Retinal circulation was restored by lowering IOP. An intraperitoneal injection of 1,000 mg/kg of DHA-ester (DHA-E) was given 5 h before the ischemia. Electroretinograms were recorded just before the ischemia and at 60-min intervals up to 4 h after circulation was restored. Results: The ratio of the amplitudes after the ischemia to that just before ischemia was significantly higher in eyes administered DHA-E than in controls at each time point (p < 0.01). Conclusion: DHA-E is effective in protecting the retina against transient retinal ischemia.

show abstract

“…Neurotoxicity by endogenous excitatory amino acids such as glutamate has been implicated as a mechanism for central (24) and retinal neuronal cell loss (29) after ischemia.…”

mentioning

confidence: 46%

Decrease of Opsin Content in the Developing Rat Photoreceptor Cells by Systemic Administration of L-Glutamate.

Kanno

Ishiguro

Shiono

et al. 1991

Cell Struct. Funct.

View full text Add to dashboard Cite

ABSTRACT. i -Gliitamate, a putative photoreceptor cell neurotransmitter, causes thinning of the inner layers of the retina and has been used for preparing biologically fractionated photoreceptor cells. However, it is possible that absence of the inner retinal layers may affect the remaining retina, and/or glutamate may directly affect photoreceptor cells. Weevaluated quantitatively the effects of i -glutamate on the developing photoreceptor cells by measuring the rod photoreceptor cell-specific protein, opsin. Wepurified rat rhodopsin and used it as the standard for measuring opsin content of rat retinas with competitive enzyme-linked immunosorbentassay. Various concentrations of glutamate were injected into 7-day-old rats, and the effects of the amino acid concentration on opsin expression were determined on postnatal day 14. Inner layers of the retina degenerated when10 ju\ or 15 ju\ of 2.4 M glutamate/gram body weight was administered subcutaneously. Opsin content of these glutamate-treated retinas decreased significantly compared with control retinas. Weadministered glutamate to rats at various stages of development and determined the effects by light microscopy on postnatal day 14. The administration of glutamate resulted in no degeneration of the inner retina if injected on postnatal day 1 or 2, degeneration of the inner retina between day 3 to 7, and again, no degeneration after postnatal day 13. Opsin content decreased significantly when glutamate was administered between postnatal day 1 to 7, but not after day 13, the day the blood-retinal barrier seems to reach maturity. Our findings indicate that systemic administration of L-glutamate affects the expression of opsin in the developing rod photoreceptor cells.Glutamate is a leading candidate for the excitatory neurotransmitter of the vertebrate retinal photoreceptors (2, 4, 10) and bipolar cells (8,15,26). Neurotoxicity by endogenous excitatory amino acids such as glutamate has been implicated as a mechanism for central (24) and retinal neuronal cell loss (29) after ischemia.Moreover, it is shown that an abnormality in the glutamate metabolism may cause a retinal dysfunction (1).Since Lucas and Newhouse(13) reported the toxic effects of glutamate on the inner retina, the amino acid has been used to prepare biologically fractionated photoreceptors since the photoreceptors appeared normal in form and concentration. The results using the fractionated photoreceptors provided important clues to amino acid levels (6), electroretinograms (21), and distribution of the enzymes (22) In the present study, to evaluate the effects of neurotoxic glutamate on the developing rat photoreceptor cells quantitatively, an assay of the rod photoreceptorspecific protein, opsin, in glutamate-administered rat retinas was carried out.

show abstract

Dextromethorphan Protects Retina Against Ischemic Injury In Vivo

Cited by 102 publications

References 11 publications

Involvement of Oxygen Free Radicals in Experimental Retinal Ischemia and the Selective Vulnerability of Retinal Damage

Involvement of Oxygen Free Radicals in Experimental Retinal Ischemia and the Selective Vulnerability of Retinal Damage

Protective Effect of Docosahexaenoic Acid against Retinal Ischemic Injury: An Electroretinographic Study

Decrease of Opsin Content in the Developing Rat Photoreceptor Cells by Systemic Administration of L-Glutamate.

Contact Info

Product

Resources

About