Electrical inhibition of lens epithelial cell proliferation: an additional factor in secondary cataract?

Abstract

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 p27 kip1 . 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.

Electrical dimensions in cell science

“…Both the cell cycle and the mitotic spindle are targets for physiological extracellular EFs Wang et al, 2005;Song et al, 2002), and regulating these might have a profound impact on the control of tumours. For example, cultured rat lens epithelial cells and bovine endothelial cells show markedly reduced proliferation rates in a physiological EF.…”

“…For example, cultured rat lens epithelial cells and bovine endothelial cells show markedly reduced proliferation rates in a physiological EF. The EF suppresses cyclin-E expression and increases expression of p27 kip1 (an inhibitor of the cyclin-E-Cdk2 complex), and consequently cells fail to make the G1-S-phase transition and undergo cell-cycle arrest Wang et al, 2005). In rat corneal epithelial cells in vivo, however, an endogenous EF enhanced proliferation and oriented the mitotic spindle (Song et al, 2002).…”

Transmembrane voltage potential controls embryonic eye patterning inXenopus laevis

“…They control cell migration (McCaig et al, 2009;Prevarskaya et al, 2010;Yao et al, 2008;Yasuda and Adams, 2010), proliferation (Blackiston et al, 2011) and differentiation (Sundelacruz et al, 2009) in a wide variety of systems. Although epithelial electric fields have been implicated in adult eye wound healing Wang et al, 2005;Zhao et al, 2006), the roles of ion flows in eye development have not been explored. In Xenopus laevis, we have uncovered an endogenous role for plasma membrane voltage gradients during eye development, and show that artificially induced changes in transmembrane potential (V mem ) are sufficient to induce well-formed eyes outside of the anterior neural field.…”

Ionic Components of Wound Current at Mouse Skin Incisional Wounds

“…Such electric fields are generated when the epithelial layer is disrupted instantaneously and the lesion short-circuits the transepithelial potential difference (2)(3)(4)(5)(6)(7). Electric currents at wounds in human skin (4,(8)(9)(10)(11) and in rodent cornea and skin (5,7,(12)(13) have been measured with various techniques, such as vibrating probes, micro-glass electrodes, micro-needle arrays, and bioelectric imagers (5,12,(14)(15)(16). For example, it is reported that a large outward current of 4 mA cm -2 was measured at the wound edges of rat cornea and human skin.…”