Wang Entong, Reid Brian, Lois Noemi, Forrester John V, McCaig Colin D, Zhao Min
Department of Biomedical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
FASEB J. 2005 May;19(7):842-4. doi: 10.1096/fj.04-2733fje. Epub 2005 Mar 11.
Cataract is the most common cause of blindness but is at least curable by surgery. Unfortunately, many patients gradually develop the complication of posterior capsule opacification (PCO) or secondary cataract. This arises from stimulated cell growth within the lens capsule and can greatly impair vision. It is not fully understood why residual lens epithelial cell growth occurs after surgery. We propose and show that cataract surgery might remove an important inhibitory factor for lens cell growth, namely electric fields. The lens generates a unique pattern of electric currents constantly flowing out from the equator and entering the anterior and posterior poles. We show here that cutting and removing part of the anterior capsule as in cataract surgery significantly decreases the equatorial outward electric currents. Application of electric fields in culture inhibits proliferation of human lens epithelial cells. This inhibitory effect is likely to be mediated through a cell cycle control mechanism that decreases entry of cells into S phase from G1 phase by decreasing the G1-specific cell cycle protein cyclin E and increasing the cyclin-Cdk complex inhibitor p27kip1. Capsulorrhexis in vivo, which reduced endogenous lens electric fields, significantly increased LEC growth. This, together with our previous findings that electric fields have significant effects on the direction of lens cell migration, points to a controlling mechanism for the aberrant cell growth in posterior capsule opacification. A novel approach to control growth of lens epithelial cells using electric fields combined with other controlling mechanisms may be more effective in the prevention and treatment of this common complication of cataract surgery.
白内障是导致失明的最常见原因,但至少可通过手术治愈。不幸的是,许多患者会逐渐出现后囊膜混浊(PCO)或继发性白内障的并发症。这是由晶状体囊内受刺激的细胞生长引起的,会严重损害视力。目前尚不完全清楚为什么手术后会出现残留晶状体上皮细胞生长。我们提出并证明,白内障手术可能会去除晶状体细胞生长的一个重要抑制因素,即电场。晶状体产生一种独特的电流模式,不断从赤道流出并进入前后极。我们在此表明,如白内障手术那样切开并去除部分前囊会显著降低赤道向外的电流。在培养中施加电场可抑制人晶状体上皮细胞的增殖。这种抑制作用可能是通过一种细胞周期控制机制介导的,该机制通过减少G1特异性细胞周期蛋白细胞周期蛋白E并增加细胞周期蛋白 - Cdk复合物抑制剂p27kip1,减少细胞从G1期进入S期。体内撕囊术减少了内源性晶状体电场,显著增加了晶状体上皮细胞(LEC)的生长。这与我们之前关于电场对晶状体细胞迁移方向有显著影响的发现一起,指出了后囊膜混浊中异常细胞生长的一种控制机制。一种将电场与其他控制机制相结合来控制晶状体上皮细胞生长的新方法,可能在预防和治疗这种常见的白内障手术并发症方面更有效。