FGF-2 counteracts loss of TGFβ affected cells from rat lens explants: Implications for PCO (after cataract)

The lens of the eye is a flattened transparent globe, through which light must pass on its way to the retina. It consists of only two cell types, elongated fiber cells covered anteriorly by a monolayer of epithelial cells. Cataract, or loss of lens transparency, accounts for about 42 percent of all blindness. Globally, more than 20 million people now have cataract, a number that may double by 2010 because of increasing life expectancy and the strong association between cataract and aging [1]. Surgery is the only treatment available at present. The preferred procedure involves removing a circular anterior portion of the lens capsule (a thick basement membrane that completely encloses the lens), breaking up and removing most of the lens tissue and placing a synthetic lens implant (intraocular lens, IOL) into the empty capsular bag that remains. While most patients benefit from this treatment initially, within 5 years of surgery about 20-40% suffer a secondary loss of vision because of posterior capsule opacification (PCO), also known as after-cataract [2]. PCO can be treated using an Nd:YAG laser; however, this procedure is not without risk to sight, adds substantially to the cost of treatment, and is not readily available in the developing world where the incidence of cataract is high [3]. PCO therefore remains a significant clinical problem. PCO arises from lens epithelial cells left behind at the time of cataract surgery [3-6]. These cells, which are initially associated only with the remnants of the anterior capsule, migrate onto the posterior capsule underlying the IOL and into the light path. Many undergo epithelial-mesenchymal transition resulting in the formation of fibroblasts and spindle-like myofibroblasts. Impairment of vision is thought to result from myofibroblast-induced wrinkling of the central region of the posterior capsule and/or formation of opaque multilayered plaques, strands, and aggregations of cells (Elschnig’s pearls) in this region [3-5]. Abundant deposition of ECM by aberrant cells may also contribute significantly to visual impairment [3]. TGF-beta (TGFβ) has been shown in vitro to initiate cellular and molecular changes in lens epithelial cells that are associated with PCO development, including myofibroblast formation, wrinkling of the lens capsule, induction of fibroblast markers, and deposition of ECM. First highlighted in studies of rat lens epithelial explants [7], this finding has since been confirmed and extended using a variety of rat, mouse, rabbit, bovine, canine, and human models, both in vitro and in vivo [8-17]. Such studies, together with others indicating that TGFβ is potentially available to lens cells in situ, point to a key role for TGFβ in the aetiology of PCO [10,16-24]. ©2004 Molecular Vision