Changes of GABA Metabolic Enzymes in Acute Retinal Ischemia

Kobayashi, Naoki; Ishiguro, Sei-ichi; Tomita, Hiroshi; Nishikawa, Shimpei; Tamai, Makoto

doi:10.1006/exer.1999.0681

Cited by 19 publications

(10 citation statements)

References 19 publications

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“…The complex interplay of these compounds was confirmed in the present study. The finding may be related to the observation that glutamate and GABA accumulate in the Müller cells secondary to retinal ischaemia (Kobayashi et al. 1999; Napper & Kalloniatis 1999).…”

Section: Discussionmentioning

confidence: 79%

The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N‐methyl‐D‐aspartate and is blocked by prostaglandin synthesis inhibition

Holmgaard

Aalkjær²,

Lambert³

et al. 2008

Acta Ophthalmologica

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ABSTRACT.Purpose: Retinal hyperperfusion resulting from disturbances in the regulation of arteriolar tone is involved in the pathophysiology of a variety of retinal diseases. The mechanisms underlying this regulation of tone involve cellular components in both the vascular wall and the perivascular tissue. However, previous in vitro studies of the influence of perivascular retinal tissue on retinal tone regulation have been hampered by the release of an endogenous relaxing factor that renders the arteriole insensitive to vasoconstrictors. The purpose of the present study was to test whether N-methyl-D-aspartate (NMDA) and c-amino butyric acid (GABA) receptors, and a cyclooxygenase (COX) product influence this effect of perivascular retinal tissue in vitro. Methods: Porcine retinal arterioles were mounted in a wire myograph for isometric force measurements. The contractile effect of the prostaglandin analogue U46619 was studied on vessels with preserved perivascular retinal tissue and after this tissue had been removed. The influence of the perivascular tissue was studied after addition of NMDA (a specific agonist for a subtype of the glutamate receptor), DL-amino-5-phosphonovaleric acid (DL-APV, an antagonist at the same receptor), the natural inhibitory transmitter GABA, and picrotoxin (an antagonist at ionotropic GABA receptors). These experiments were made in the absence and presence of the COX inhibitor, ibuprofen. Results: U46619 caused a concentration-dependent contraction of isolated retinal arterioles. This vasoconstriction was significantly smaller in the presence of perivascular tissue. The NMDA-receptor antagonist, DL-APV, reduced this attenuating influence of the perivascular tissue on the response to U46619, and the response could be modified by NMDA and GABA, but not by picrotoxin. However, ibuprofen totally blocked the attenuating influence of the perivascular tissue on the response to U46619. Conclusions: The inhibition of vascular contractility induced by perivascular retinal tissue in vitro involves NMDA-receptors and an effect of GABA-mimetic substance on retinal tissue. The generation of these effects involves a COX product.

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Section: Discussionmentioning

confidence: 79%

The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N‐methyl‐D‐aspartate and is blocked by prostaglandin synthesis inhibition

Holmgaard

Aalkjær²,

Lambert³

et al. 2008

Acta Ophthalmologica

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“…The glial GABA uptake may also indirectly be affected under pathological conditions. In diabetic and ischemic rat retinae, GABA rapidly accumulates in Mü ller cells (Ishikawa et al, 1996;Napper et al, 2001) due to a decrease of the GABA transaminase activity (Kobayashi et al, 1999). Such an intracellular GABA accumulation should (further) impair the efficiency of the GABA uptake into Mü ller cells due to a decreased driving force.…”

Section: Discussionmentioning

confidence: 98%

High‐affinity GABA uptake in retinal glial (Müller) cells of the guinea pig: Electrophysiological characterization, immunohistochemical localization, and modeling of efficiency

Biedermann

Bringmann

Reichenbach

2002

Glia

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Glial cells may act as important modulators of neuronal information processing, in particular, via fast uptake of neuronally released transmitters. Here, we characterize the electrogenic gamma-aminobutyric acid (GABA) transporters present in the plasma membranes of Müller (glial) cells of the guinea pig retina and present an estimate of their functional efficiency. The GABA-evoked whole-cell currents are voltage-dependent, with increasing amplitudes and decreasing affinity constants at more negative membrane potentials. The transmembranal GABA transport is concentration-dependent, with near-maximal currents at 100 microM GABA, and is dependent on extracellular sodium and chloride ions; the stoichiometry is 1 GABA/2 Na(+)/1 Cl(-). Immunohistochemical labeling and whole-cell voltage-clamp records reveal that Müller cells express both GAT-1 and GAT-3 (but not GAT-2), and that the transporter proteins are expressed predominantly at plasma membrane sites that, in situ, are localized in the outer retina where GABA uptake is performed exclusively by Müller cells. When extracellular GABA enters the cell interior, it evokes, via activation of the GABA transaminase, an NAD(P)H fluorescence signal selectively in the distal region of the Müller cells where their mitochondria are located. Using our experimental data, we simulated the GABA clearance from the extracellular space surrounding one Müller cell; these estimates show that a pulse of 100 microM extracellular GABA is fully cleared after 70 ms. It is suggested that Müller cells may be involved in the regulation of GABAergic transmission within the retina by providing a fast termination of GABAergic signaling via their highly efficient GABA uptake.

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“…So far, some evidence for an impairment of the highly GABAergic amacrine cells, diminished cone system activity, Müller cells damage and other forms of retinopathy due to VGB has been found (Steinhoff et al 1997;Butler et al 1987;Krauss et al 1998;Arndt et al 1999;Daneshvar et al 1999) but more research is necessary. Probably some similarity may exist with retinal ischemia where an accumulation of GABA in Müller cells has been attributed to a decreased level of GABAtransaminase (Kobayashi et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Visual field defects in patients taking vigabatrin

Midelfart¹,

Midelfart²,

Brodtkorb

2000

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To investigate visual field loss in patients on long-term treatment with the antiepileptic drug vigabatrin, recently reported to cause visual disturbances. Methods: Eighteen patients taking vigabatrin for 0.5-9.5 years were examined with automated perimetry up to 60ae from fixation using the Humphrey Field Analyser. Five patients with epilepsy receiving other medications served as controls. Patients found to have a visual field defect underwent ophthalmologic examination. Results: Among the 18 patients in the vigabatrin group, visual field defects categorised as mild were revealed in 6 right eyes (33%) and 8 left eyes (44.4%), while defects categorised as severe were found in 9 right eyes (50%) and 8 left eyes (44.4%). The majority of the defects (66.7% in the right eye) were peripheral constriction with nasal predominance. The location of the defects was confirmed in 8 patients also tested with Kowa AP340 perimetry. Conclusion: According to our results, visual field defects among the patients on vigabatrin therapy may occur more frequently than previously recognised. V igabatrin (VGB) is an effective antiepileptic drug acting as a relatively specific irreversible inhibitor of gammaaminobutyric acid (GABA) transaminase. Inhibition of this enzyme produces an elevation of GABA concentrations in the brain associated with anticonvulsant effect (Mattson et al. 1994;Petroff et al. 1996aPetroff et al. , 1996bAvanzini et al. 1997). No abnormalities in central nervous system conduction related to VGB treatment in humans have been observed (Mauguière et al. 1997). In the vertebrate retina, GABA is one of the most important inhibitory transmitters (Berman 1991).Currently, VGB has been used for more than 12 years for treatment of partial seizures (Marson et al. 1997). It was found to be less effective, but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies (Chadwick 1999). Recently, several reports have documented persistent visual field defects in patients with long-term use of VGB, either as monotherapy or concurrently with other antiepileptic drugs (Blackwell et al. 1997;Eke et al. 1997;Harding 1997;Wilson & Brodie 1997;Wong et al. 1997;Williams & Brennan 1997;Krauss et al. 1998;Ruether et al. 1998;Daneshvar et al. 1999;Kälviäinen et al. 1999;Wilton et al. 1999). According to these, VGB seems to increase the risk of a unique and specific pattern of bilateral, mainly asymptomatic visual field constriction (Kälviäin-en et al. 1999). The incidence of these visual field defects was recently found to be substantially higher than previously assumed. A frequency as high as 40% (9% mild, 31% severe) among patients on VGB monotherapy has been reported (Kälviäinen et al. 1999). Any clear risk factors regarding age, duration of the treatment, the dosage or the cumulative amount of VBG consumed during the treatment were not found (Kälviäinen et al. 1999;Daneshvar et al. 1999). Unfortunately, irreversible visual field defects after cessation of the VGB therapy...

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Changes of GABA Metabolic Enzymes in Acute Retinal Ischemia

Cited by 19 publications

References 19 publications

The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N‐methyl‐D‐aspartate and is blocked by prostaglandin synthesis inhibition

The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N‐methyl‐D‐aspartate and is blocked by prostaglandin synthesis inhibition

High‐affinity GABA uptake in retinal glial (Müller) cells of the guinea pig: Electrophysiological characterization, immunohistochemical localization, and modeling of efficiency

Visual field defects in patients taking vigabatrin

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