近日,，《生物化學(xué)和生物物理研究通訊》(Biochemical and Biophysical Research Communications )雜志在線發(fā)表了新澤西州（UMDNJ）醫(yī)學(xué)和牙科大學(xué)以及哥倫比亞大學(xué)的研究人員的發(fā)現(xiàn)，眼球晶狀體也存在腦部最常見的主要神經(jīng)遞質(zhì)受體,，這一發(fā)現(xiàn)可能有助于解釋白內(nèi)障,、癲癇和臨床抗癲癇和抗抑郁藥物使用之間的聯(lián)系。
“最近的研究發(fā)現(xiàn)了白內(nèi)障增加和癲癇之間的關(guān)聯(lián),，研究顯示使用抗癲癇藥物以及一些常用抗抑郁藥增加白內(nèi)障患病率”,，通訊作者UMDNJ - 新澤西醫(yī)學(xué)院的Peter Frederikse博士解釋說,。 “聯(lián)系這些觀察結(jié)果的共同點是，我們的研究表明,，大腦中最普遍的神經(jīng)遞質(zhì)受體也存在于晶狀體中,。”
該研究小組包括哥倫比亞大學(xué)梅爾曼公共衛(wèi)生學(xué)院的Norman Kleiman博士、新澤西醫(yī)學(xué)院的Mohammed Farooq和新澤西州牙科學(xué)院的Rajesh Kaswala, DDS和Chinnaswamy Kasinathan博士,，研究發(fā)現(xiàn)谷氨酸受體蛋白,，特別是重要的GluA2亞基，表達(dá)于晶狀體,，其調(diào)節(jié)方式與在腦部的調(diào)節(jié)方式驚人相似,。在神經(jīng)系統(tǒng)中，谷氨酸和GluA受體蛋白是記憶形成和情緒調(diào)節(jié)的基礎(chǔ),，是癲癇發(fā)病的重要因素,。與此相一致，這些受體蛋白也是多種抗癲癇藥物和抗抑郁藥物的靶點,。
“晶狀體存在這些谷氨酸受體,，表明它們可能是腦疾病和白內(nèi)障之間的聯(lián)系，是現(xiàn)有藥物非預(yù)期的次要靶點”,，F(xiàn)rederikse說,。我們現(xiàn)在的目的是利用這些信息解析出抗癲癇藥物和抗抑郁藥對于晶狀體這些靶點以外部位的潛在影響，并研究谷氨酸受體在晶狀體生物學(xué)和病理學(xué)中的作用,。”
這項研究由國立衛(wèi)生研究院國立眼科研究所資助,。(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.
