Is reduced ornithine-δ-aminotransferase activity the cause of vigabatrin-associated visual field defects?
Is reduced ornithine-δ-aminotransferase activity the cause of vigabatrin-associated visual field defects?
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DOI：
10.1016/j.eplepsyres.2010.08.006
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发表时间：
2010-11-01
影响因子：
2.2
通讯作者：
Kalviainen, Reetta
中科院分区：
文献类型：
--
作者：
Sorri, Iiris;Brigell, Mitchell G.;Kalviainen, Reetta
背景：GABA能抗癫痫药物VGB可导致30-40%的患者出现双侧同心性视野缺陷(VFD)。虽然VFDs的临床和电生理特征已有很好的文献记载，但其视网膜毒性的机制仍不清楚。目的：确定基础鸟氨酸-β-氨基转移酶(OAT)活性降低是否与VGB视网膜毒性的病因有关，从而导致轻度回复型萎缩。方法：检测淋巴细胞OAT活性和血小板GABA转氨酶活性，并测定血浆GABA、鸟氨酸、赖氨酸、谷氨酸和谷氨酰胺水平，并进行视野检查。共有47名年龄在14-78岁的受试者接受了检查。21例癫痫患者停用VGB超过1年，11例出现VGB诱发的VFD，10例视野正常。10名癫痫患者目前接受VGB治疗超过1年；4名患者患有VGB诱发的VFD，6名患者的视野正常。结果：与10例服用替加宾的癫痫患者和6例脑回萎缩(GA)患者及6例有VFD的患者相比，VFD患者的OAT活性显著降低(77.4pmolP5C/min/mgPro比181.9 pmolP5C/nNIN/mgPro，p=0.002)。在接受VGB治疗的患者中，有无VFD的患者之间没有发现差异(149.4 pmolP5C/min/mgPro对159.1 pmolP5C/min/mgPro)。
Background: A gabaergic antiepileptic drug, vigabatrin (VGB), is known to induce bilateral concentric visual field defects (VFD) in 30-40% of treated patients. Although the clinical and electrophysiological features of VFDs are well documented, the mechanism of retinal toxicity is still unclear.Purpose: To determine if low basal ornithine-delta-aminotranspherase (OAT) activity is implicated in the etiology of VGB retinotoxicity, resulting in a phenotype of a mild form of gyrate atrophy.Methods: Assays of OAT activity in lymphocytes and GABA-transaminase activity in platelets were performed, and plasma levels of GABA, ornithine, lysine, glutamic acid and glutamine were measured, and visual fields were examined. A total of 47 subjects, aged 14-78 years, were examined. Twenty-one epileptic patients were off VGB more than 1 year; 11 patients with VGB-induced VFD and 10 with normal visual fields. Ten epileptic patients were on current VGB therapy more than 1 year; four patients with VGB-induced VFD and six with normal visual fields. The results were compared with those of 10 epilepsy patients taking tiagabine and six patients who suffered from gyrate atrophy (GA) or were obligate carriers of the disease.Results: In patients who had stopped VGB and who had VFDs, OAT activity was significantly reduced as compared with those who had normal visual fields (77.4 pmol P5C/min/mgPro vs. 181.9 pmol P5C/nnin/mgPro, p= 0.002). In patients with ongoing VGB therapy, no difference was found between the patients with and without VFDs (149.4 pmol P5C/min/mgPro vs. 159.1 pmol P5C/min/mgPro).