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Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death

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Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death. / Vorwerk, C K; Naskar, R; Schuettauf, F; Quinto, K; Zurakowski, D; Gochenauer, G; Robinson, M B; Mackler, S A; Dreyer, E B.

In: INVEST OPHTH VIS SCI, Vol. 41, No. 11, 10.2000, p. 3615-21.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Vorwerk, CK, Naskar, R, Schuettauf, F, Quinto, K, Zurakowski, D, Gochenauer, G, Robinson, MB, Mackler, SA & Dreyer, EB 2000, 'Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death', INVEST OPHTH VIS SCI, vol. 41, no. 11, pp. 3615-21.

APA

Vorwerk, C. K., Naskar, R., Schuettauf, F., Quinto, K., Zurakowski, D., Gochenauer, G., Robinson, M. B., Mackler, S. A., & Dreyer, E. B. (2000). Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death. INVEST OPHTH VIS SCI, 41(11), 3615-21.

Vancouver

Vorwerk CK, Naskar R, Schuettauf F, Quinto K, Zurakowski D, Gochenauer G et al. Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death. INVEST OPHTH VIS SCI. 2000 Oct;41(11):3615-21.

Bibtex

@article{9b12ba9452824eddb9ebf5f5acd26c27,
title = "Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death",
abstract = "PURPOSE: Elevated levels of extracellular glutamate have been implicated in the pathophysiology of neuronal loss in both central nervous system and ophthalmic disorders, including glaucoma. This increase in glutamate may result from a failure of glutamate transporters (molecules that ordinarily regulate extracellular glutamate; E:xcitatory A:mino A:cid T:ransporter; EAAT). Elevated glutamate levels can also lead to alterations in glutamate receptor expression. It was hypothesized that selective blockade of glutamate transporters would be toxic to retinal ganglion cells.METHODS: Glutamate transporters were blocked either pharmacologically or with subtype-specific antisense oligonucleotides against EAAT1. Glutamate levels, transporter levels and ganglion cell survival were assayed.RESULTS: Pharmacological inhibition of glutamate transporters with either an EAAT2 specific inhibitor or a nonspecific inhibitor of all the subtypes of transporters was toxic to ganglion cells. Treatment with oligonucleotides against the glutamate transporter EAAT1 decreased the levels of expression of the transporter, increased vitreal glutamate, and was toxic to ganglion cells.CONCLUSIONS: These results demonstrate that normal function of EAAT1 and EAAT2 is necessary for retinal ganglion cell survival and plays an important role in retinal excitotoxicity. Manipulation of retinal glutamate transporter expression may become a useful tool in understanding retinal neuronal loss.",
keywords = "ATP-Binding Cassette Transporters/antagonists & inhibitors, Amino Acid Transport System X-AG, Animals, Blotting, Western, Cell Death, Chromatography, High Pressure Liquid, DNA Primers/chemistry, Dicarboxylic Acids/pharmacology, Excitatory Amino Acid Transporter 2, Glutamic Acid/metabolism, Kainic Acid/analogs & derivatives, Neurotransmitter Uptake Inhibitors/pharmacology, Oligonucleotides, Antisense/pharmacology, Pyrrolidines/pharmacology, Rats, Rats, Long-Evans, Receptors, Neurotransmitter/antagonists & inhibitors, Retinal Ganglion Cells/pathology, Vitreous Body/metabolism",
author = "Vorwerk, {C K} and R Naskar and F Schuettauf and K Quinto and D Zurakowski and G Gochenauer and Robinson, {M B} and Mackler, {S A} and Dreyer, {E B}",
year = "2000",
month = oct,
language = "English",
volume = "41",
pages = "3615--21",
journal = "INVEST OPHTH VIS SCI",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death

AU - Vorwerk, C K

AU - Naskar, R

AU - Schuettauf, F

AU - Quinto, K

AU - Zurakowski, D

AU - Gochenauer, G

AU - Robinson, M B

AU - Mackler, S A

AU - Dreyer, E B

PY - 2000/10

Y1 - 2000/10

N2 - PURPOSE: Elevated levels of extracellular glutamate have been implicated in the pathophysiology of neuronal loss in both central nervous system and ophthalmic disorders, including glaucoma. This increase in glutamate may result from a failure of glutamate transporters (molecules that ordinarily regulate extracellular glutamate; E:xcitatory A:mino A:cid T:ransporter; EAAT). Elevated glutamate levels can also lead to alterations in glutamate receptor expression. It was hypothesized that selective blockade of glutamate transporters would be toxic to retinal ganglion cells.METHODS: Glutamate transporters were blocked either pharmacologically or with subtype-specific antisense oligonucleotides against EAAT1. Glutamate levels, transporter levels and ganglion cell survival were assayed.RESULTS: Pharmacological inhibition of glutamate transporters with either an EAAT2 specific inhibitor or a nonspecific inhibitor of all the subtypes of transporters was toxic to ganglion cells. Treatment with oligonucleotides against the glutamate transporter EAAT1 decreased the levels of expression of the transporter, increased vitreal glutamate, and was toxic to ganglion cells.CONCLUSIONS: These results demonstrate that normal function of EAAT1 and EAAT2 is necessary for retinal ganglion cell survival and plays an important role in retinal excitotoxicity. Manipulation of retinal glutamate transporter expression may become a useful tool in understanding retinal neuronal loss.

AB - PURPOSE: Elevated levels of extracellular glutamate have been implicated in the pathophysiology of neuronal loss in both central nervous system and ophthalmic disorders, including glaucoma. This increase in glutamate may result from a failure of glutamate transporters (molecules that ordinarily regulate extracellular glutamate; E:xcitatory A:mino A:cid T:ransporter; EAAT). Elevated glutamate levels can also lead to alterations in glutamate receptor expression. It was hypothesized that selective blockade of glutamate transporters would be toxic to retinal ganglion cells.METHODS: Glutamate transporters were blocked either pharmacologically or with subtype-specific antisense oligonucleotides against EAAT1. Glutamate levels, transporter levels and ganglion cell survival were assayed.RESULTS: Pharmacological inhibition of glutamate transporters with either an EAAT2 specific inhibitor or a nonspecific inhibitor of all the subtypes of transporters was toxic to ganglion cells. Treatment with oligonucleotides against the glutamate transporter EAAT1 decreased the levels of expression of the transporter, increased vitreal glutamate, and was toxic to ganglion cells.CONCLUSIONS: These results demonstrate that normal function of EAAT1 and EAAT2 is necessary for retinal ganglion cell survival and plays an important role in retinal excitotoxicity. Manipulation of retinal glutamate transporter expression may become a useful tool in understanding retinal neuronal loss.

KW - ATP-Binding Cassette Transporters/antagonists & inhibitors

KW - Amino Acid Transport System X-AG

KW - Animals

KW - Blotting, Western

KW - Cell Death

KW - Chromatography, High Pressure Liquid

KW - DNA Primers/chemistry

KW - Dicarboxylic Acids/pharmacology

KW - Excitatory Amino Acid Transporter 2

KW - Glutamic Acid/metabolism

KW - Kainic Acid/analogs & derivatives

KW - Neurotransmitter Uptake Inhibitors/pharmacology

KW - Oligonucleotides, Antisense/pharmacology

KW - Pyrrolidines/pharmacology

KW - Rats

KW - Rats, Long-Evans

KW - Receptors, Neurotransmitter/antagonists & inhibitors

KW - Retinal Ganglion Cells/pathology

KW - Vitreous Body/metabolism

M3 - SCORING: Journal article

C2 - 11006260

VL - 41

SP - 3615

EP - 3621

JO - INVEST OPHTH VIS SCI

JF - INVEST OPHTH VIS SCI

SN - 0146-0404

IS - 11

ER -