Expression and localization of enzymes of arginine metabolism in the rat eye

Koshiyama, Yasuo; Gotoh, Tomomi; Miyanaka, Kei; Kobayashi, Tatsuhiko; Negi, Akira; Mori, Masataka

doi:10.1076/0271-3683(200004)20:4;1-5;ft313

Cited by 4 publications

(9 citation statements)

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“…Among the arginase isoforms, arginase II is expressed in many ocular tissues in control rats, in agreement with our previous results (Koshiyama et al, 2000). It is not induced during EIU development.…”

Section: Discussionsupporting

confidence: 92%

“…Signi®cance of NO (and iNOS) during the development of uveitis is supported by the ®ndings that treatment with NOS inhibitors such as aminoguanidine (Tilton et al, 1994), N G -nitro-L-arginine (L-NNA) (Mandai et al, 1994), and N G -nitro-L-arginine methyl ester (L-NAME) (Parks et al, 1994;Goureau et al, 1995) prevents pathological signs of uveitis. We reported intraocular localization of arginine metabolic enzymes in rat eye under normal conditions (Koshiyama et al, 2000). However, little is known on expression of the arginine recycling enzymes and arginase in eyes under pathological conditions.…”

Section: Introductionmentioning

confidence: 98%

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Coinduction of Nitric Oxide Synthase and Arginine Metabolic Enzymes in Endotoxin-induced Uveitis Rats

Koga

Koshiyama

Gotoh

et al. 2002

Experimental Eye Research

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 98%

Coinduction of Nitric Oxide Synthase and Arginine Metabolic Enzymes in Endotoxin-induced Uveitis Rats

Koga

Koshiyama

Gotoh

et al. 2002

Experimental Eye Research

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“…In contrast, arginine levels were dramatically increased in Müller cells following GS inhibition. Given that the brain and retina do not have a urea cycle and remove excess nitrogen via GS amidation of glutamate (Koshiyama et al. 2000; Wiesinger 2001), the likely explanation is a ‘flow back’ effect secondary to altered glutamate catabolism.…”

Section: Discussionmentioning

confidence: 99%

“…2000; Wiesinger 2001), the likely explanation is a ‘flow back’ effect secondary to altered glutamate catabolism. Arginine is metabolized via two pathways in the retina: one using nitric oxide synthatase (EC 1.14.13.9) to produce nitric oxide and the second via arginase (EC 3.5.3.1) to produce ornithine (Koshiyama et al. 2000).…”

Section: Discussionmentioning

confidence: 99%

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Glutamate metabolic pathways and retinal function

Bui

Acosta

et al. 2009

Journal of Neurochemistry

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Glutamate is a major neurotransmitter in the CNS but is also a key metabolite intimately coupled to amino acid production/degradation. We consider the effect of inhibition of two key glutamate metabolic enzymes: glutamine synthetase (GS) and aspartate aminotransferase on retinal function assessed using the electroretinogram to consider photoreceptoral (a‐wave) and post‐receptoral (b‐wave) amplitudes. Quantitative immunocytochemistry was used to assess amino acid levels within photoreceptors, ganglion and Müller cells secondary to GS inhibition. Intravitreal injections of methionine sulfoximine reduced GS immunoreactivity in the rat retina. Additionally, glutamate and its precursor aspartate was reduced in photoreceptors and ganglion cells, but elevated in Müller cells. This reduction in neuronal glutamate was consistent with a deficit in neurotransmission (−75% b‐wave reduction). Exogenous glutamine supply completely restored the b‐wave, whereas other amino acid substrates (lactate, pyruvate, α‐ketoglutarate, and succinate) only partially restored the b‐wave (16–20%). Inhibition of the aminotranferases using aminooxyacetic acid had no effect on retinal function. However, aminooxyacetic acid application after methionine sulfoximine further reduced the b‐wave (from −75% to −92%). The above data suggest that de novo glutamate synthesis involving aspartate aminotransferase can partially sustain neurotransmission when glutamate recycling is impaired. We also show that altered glutamate homeostasis results in a greater change in amino acid distribution in ganglion cells compared with photoreceptors.

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Retinal risks of high-dose ornithine supplements: a review

2011

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We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH 3 detoxification in the hyperornithinaemia -hyperammonaemia -homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 mmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 mmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Blood ornithine levels below 250 mmol/l do not produce retinal alteration. We concluded that short-term, low-dose or transient high-dose ornithine intake is safe for the retina; its nutritional usefulness and effect on NH 3 detoxification are supported by many researchers, but the effect may be limited; and long-term, high-dose ornithine intake may be risky for the retina. Patients with GA should avoid taking ornithine; amino acid supplementation should be administered carefully for patients with the HHH syndrome, relatives of patients with GA (heterozygotes) and subjects with RPE lesions; and blood ornithine levels and retinal conditions should be evaluated in individuals taking long-term, high-dose ornithine.

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Expression and localization of enzymes of arginine metabolism in the rat eye

Cited by 4 publications

References 0 publications

Coinduction of Nitric Oxide Synthase and Arginine Metabolic Enzymes in Endotoxin-induced Uveitis Rats

Coinduction of Nitric Oxide Synthase and Arginine Metabolic Enzymes in Endotoxin-induced Uveitis Rats

Glutamate metabolic pathways and retinal function

Retinal risks of high-dose ornithine supplements: a review

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