Artikel
Changes in kynurenic acid synthesis and expression of L-kynurenine aminotransferases in retinal ageing and neurodegeneration
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Veröffentlicht: | 18. Juni 2008 |
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Gliederung
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Background: The kynurenine aminotransferases KAT I, KAT II and KAT III are pivotal to the synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor antagonist and neuroprotectant.
Methods and results: We have found KAT I and II in the avian, rodent, and human retina and have documented expression of KAT I in Müller cell endfeet and KAT II and KAT III in retinal ganglion cells. We have also found developmental changes in KAT expression and KYNA concentrations in the avian and rodent retina. Studies of retinal neurodegeneration with animal models have shown alterations in KYNA synthesis in the retina in response to retinal ganglion cell loss. We have found an age-dependent decrease of retinal KYNA and kynurenine aminotransferases in DBA/2J mice, a model of ocular hypertension. Recently, we also found KAT I, II and III immunoreactivity in corpora amylacea (CAm) in the human retina as a hallmark of ageing and degeneration.
Conclusions: KAT I, KAT II, and KAT III and changes in KYNA formation may all be involved in the mechanisms of retinal ageing and neurodegeneration. There is a need for further studies on pharmacological modulation of the metabolic pathway as a strategy against neurodegenerative retinal diseases.