近日，《生物化学和生物物理研究通讯》(Biochemical and Biophysical Research Communications )杂志在线发表了新泽西州（UMDNJ）医学和牙科大学以及哥伦比亚大学的研究人员的发现，眼球晶状体也存在脑部最常见的主要神经递质受体，这一发现可能有助于解释白内障、癫痫和临床抗癫痫和抗抑郁药物使用之间的联系。
“最近的研究发现了白内障增加和癫痫之间的关联，研究显示使用抗癫痫药物以及一些常用抗抑郁药增加白内障患病率”，通讯作者UMDNJ - 新泽西医学院的Peter Frederikse博士解释说。 “联系这些观察结果的共同点是，我们的研究表明，大脑中最普遍的神经递质受体也存在于晶状体中。”
该研究小组包括哥伦比亚大学梅尔曼公共卫生学院的Norman Kleiman博士、新泽西医学院的Mohammed Farooq和新泽西州牙科学院的Rajesh Kaswala, DDS和Chinnaswamy Kasinathan博士，研究发现谷氨酸受体蛋白，特别是重要的GluA2亚基，表达于晶状体，其调节方式与在脑部的调节方式惊人相似。在神经系统中，谷氨酸和GluA受体蛋白是记忆形成和情绪调节的基础，是癫痫发病的重要因素。与此相一致，这些受体蛋白也是多种抗癫痫药物和抗抑郁药物的靶点。
“晶状体存在这些谷氨酸受体，表明它们可能是脑疾病和白内障之间的联系，是现有药物非预期的次要靶点”，Frederikse说。我们现在的目的是利用这些信息解析出抗癫痫药物和抗抑郁药对于晶状体这些靶点以外部位的潜在影响，并研究谷氨酸受体在晶状体生物学和病理学中的作用。”
这项研究由国立卫生研究院国立眼科研究所资助。(生物谷Bioon.com)
doi:10.1016/j.bbrc.2012.01.009
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GluA2 AMPA glutamate receptor subunit exhibits codon 607 Q/R RNA editing in the lens
Mohammed Farooq, Rajesh H. Kaswala, Norman J. Kleiman, Chinnaswamy Kasinathan, Peter H. Frederikse
Regulated GluA2 AMPA receptor subunit expression, RNA editing, and membrane localization are fundamental determinants of neuronal Ca2+ influx, and underlie basic functions such as memory and the primary brain disorder epilepsy. Consistent with this, AMPARs, and specifically GluA2, are targets of common antiepileptic drugs (AEDs) and antidepressants. Recently, epidemiological associations between epilepsy and increased cataract prevalence were found comparable to cataract links with diabetes and smoking. Similarly, use of AEDs and several antidepressants also showed links with increased cataract. Here, we demonstrated GluA2 in lenses, consistent with REST/NRSF and REST4 we described previously in lenses, as well as GluA1 and ADAR2 in the lens. Surprisingly, we found predominant neuron-like Q/R editing of GluA2 RNAs also occurs in the lens and evidence of lens GluA2 phosphorylation and STEP phosphatases linked with GluA2 membrane localization in neurons. This study is among the first to show GluA2 expression and predominant Q/R RNA editing in a non-neural cell. Our results suggest GluA2 AMPARs have related roles in lens physiology and disease processes, and provide evidence these anticonvulsant and antidepressant drug targets also occur in the lens.
