Bora Puran S, Kaliappan Sankaranarayanan, Xu Qin, Kumar Shalesh, Wang Yali, Kaplan Henry J, Bora Nalini S
Department of Ophthalmology and Visual Science, Kentucky Lions Eye Center, University of Louisville, KY, USA.
FEBS J. 2006 Apr;273(7):1403-14. doi: 10.1111/j.1742-4658.2006.05163.x.
One of the pathologic complications of exudative (i.e. wet-type) age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The aim of this study was to investigate whether chronic and heavy alcohol consumption influenced the development of CNV in a rat model. The oxidative metabolism of alcohol is minimal or absent in the eye, so that ethanol is metabolized via a nonoxidative pathway to form fatty acid ethyl esters (FAEE). Fatty acid ethyl ester synthase (FAEES) was purified from the choroid of Brown Norway (BN) rats. The purified protein was 60 kDa in size and the antibody raised against this protein showed a single band on western blot. BN rats on a regular diet were fed alcohol for 10 weeks. Control rats were fed water with a regular diet and pair-fed control rats were fed regular diet, water and glucose. We found that FAEES activity was increased 4.0-fold in the choroid of alcohol-treated rats compared with controls. The amount of ethyl esters produced in the choroid of 10 week alcohol-fed rats was 7.4-fold more than rats fed alcohol for 1 week. The increased accumulation of ethyl esters was associated with a 3.0-fold increased expression of cyclin E and cyclin E/CDK2; however, the level of the cyclin kinase inhibitor, p27Kip, did not change. The increased accumulation of ethyl esters was also associated with 3.0-fold decreased expression of APN in the choroid. We also found that the size of CNV increased by 28% in alcohol-fed rats. Thus, our study showed that chronic, heavy alcohol intake was associated with both an increased accumulation of ethyl esters in the choroid and an exacerbation of the CNV induced by laser treatment. These results may provide insight into the link between heavy alcohol consumption and exudative AMD.
渗出性（即湿性）年龄相关性黄斑变性（AMD）的病理并发症之一是脉络膜新生血管（CNV）。本研究的目的是调查长期大量饮酒是否会影响大鼠模型中CNV的发展。眼睛中酒精的氧化代谢极少或不存在，因此乙醇通过非氧化途径代谢形成脂肪酸乙酯（FAEE）。从褐家鼠（BN）的脉络膜中纯化出脂肪酸乙酯合酶（FAEES）。纯化后的蛋白质大小为60 kDa，针对该蛋白质产生的抗体在蛋白质印迹上显示出一条单带。正常饮食的BN大鼠喂食酒精10周。对照大鼠喂食常规饮食的水，配对喂养的对照大鼠喂食常规饮食、水和葡萄糖。我们发现，与对照组相比，酒精处理大鼠脉络膜中的FAEES活性增加了4.0倍。喂食酒精10周的大鼠脉络膜中产生的乙酯量比喂食酒精1周的大鼠多7.4倍。乙酯积累的增加与细胞周期蛋白E和细胞周期蛋白E/细胞周期蛋白依赖性激酶2（CDK2）的表达增加3.0倍相关；然而，细胞周期蛋白激酶抑制剂p27Kip的水平没有变化。乙酯积累的增加还与脉络膜中氨肽酶N（APN）的表达降低3.0倍相关。我们还发现，喂食酒精的大鼠中CNV的大小增加了28%。因此，我们的研究表明，长期大量饮酒与脉络膜中乙酯积累的增加以及激光治疗诱导的CNV恶化均相关。这些结果可能为大量饮酒与渗出性AMD之间的联系提供见解。
