犬尿氨酸酸和犬尿氨酸氨基转移酶在视网膜衰老和神经退行性变中的作用。

Kynurenic acid and kynurenine aminotransferases in retinal aging and neurodegeneration.

机构信息

Centre for Ophthalmology, University of Tübingen, Roentgenweg 11, D-72076 Tübingen, Germany.

出版信息

Pharmacol Rep. 2011;63(6):1324-34. doi: 10.1016/s1734-1140(11)70697-1.

Abstract

The kynurenine aminotransferases (KATs) KAT I and KAT II are pivotal to the synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor antagonist and neuroprotectant. KAT I and II have been found in avian, rodent, and human retina. Expression of KAT I in Müller cell endfeet and KAT II in retinal ganglion cells has been documented. Developmental changes in KAT expression and KYNA concentration in the avian and rodent retina have also been found. Studies of retinal neurodegeneration have shown alterations in KYNA synthesis in the retina in response to retinal ganglion cell loss. In DBA/2J mice, a model of ocular hypertension, an age-dependent decrease of retinal KYNA and KATs was found. In the corpora amylacea in the human retina intensive KAT I and II immunoreactivity was demonstrated. In summary, these findings point to the potential involvement of KYNA in the mechanisms of retinal aging and neurodegeneration.

摘要

犬尿氨酸氨基转移酶（KAT）I 和 KAT II 是犬尿氨酸（KYNA）合成的关键酶，KYNA 是唯一已知的内源性谷氨酸受体拮抗剂和神经保护剂。KAT I 和 KAT II 已在禽类、啮齿类和人类视网膜中被发现。已经证明 KAT I 在 Muller 细胞终足中表达，KAT II 在视网膜神经节细胞中表达。在禽类和啮齿类动物视网膜中还发现了 KAT 表达和 KYNA 浓度的发育变化。视网膜神经退行性变的研究表明，在视网膜神经节细胞丧失的情况下，KYNA 的合成发生了改变。在 DBA/2J 小鼠，一种眼压升高的模型中，发现视网膜 KYNA 和 KATs 随年龄的增长而减少。在人类视网膜的淀粉样体中，强烈的 KAT I 和 KAT II 免疫反应被证明。总之，这些发现表明 KYNA 可能参与了视网膜衰老和神经退行性变的机制。