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It is now widely recognised that posterior capsule opacification (PCO) results from the proliferation and migration of lens epithelial cells (LECs) across the posterior capsule and is the most common cause of reduced visual acuity following modern cataract surgery.1 2 If strategies to prevent PCO are to be developed in a rational way then it will be necessary to understand the mechanisms underlying this relatively aggressive cell growth. Recently, significant advances have been made in the technologies that are required, on the one hand to study the basic molecular mechanisms of growth in vitro,3-5 and on the other to follow the patterns of cell movements within the capsular bag in vivo.6
The recent in vitro studies based on a human capsular bag model have led to a sea change in our views on the forces driving lens cell growth. Formerly it was held that lens cell growth could not be sustained without the addition of external growth factors and this led to an extensive search to define these exogenous factors (see Reid7 for a review). However, most of these studies were carried out on lens cells cultured on plastic. Wormstone and colleagues5 have now shown that cells that remain in the capsular bag after surgery do not require factors exported from other cell types in order to survive and grow. They will rapidly cover the posterior capsule, induce wrinkling and cell aggregation and, indeed, produce many of the classic manifestations of PCO without any external influence. Furthermore, cells within young (<40 years) capsular bags show more aggressive cell proliferation than that displayed by older cells (>60 years) and this again mirrors the clinical situation.8 These recent data show that lens cells control growth within the capsular bag and this, in turn, has led to a search for autocrine growth factors. Preliminary analyses of the growth factors contained within capsular bags cultured for more than 100 days in a medium without additions9 indicate that lens cells can produce a range of growth factors including hepatocyte growth factor (HGF) and fibroblast growth factor (FGF). The presence of these growth factors is particularly interesting as both promote the proliferation and migration of epithelial cells.10 11
In vitro studies of human capsular bags with implanted PMMA lenses have also revealed that the matrix on which the cells are growing has a great effect on proliferation and migration.5 Cell movement onto the intraocular lens (IOL) is much more tentative than progression across the posterior capsule and cell regression is much more likely to occur. In fact, a certain degree of cell regression also occurs on the posterior capsule, especially once prominent wrinkles have formed and cell regression may hold the key as to why PCO presents as a serious visual problem for some patients but not for others.
Cell progression and regression can now be followed in vivo and Hollick and her colleagues show, in this issue of the BJO (p1182), that both aspects of cell behaviour depend on the material of the IOL. Most importantly, although cell growth and migration occurred in most cases over the first few weeks following cataract surgery, cell regression was found to occur over the following 2 years in 80% of patients receiving polyacrylic IOLs. This compared with regression rates of 8% and 15% for silicone and PMMA lenses respectively. The authors put forward several plausible explanations as to why this difference should occur. There does appear to be a stronger interaction between the capsule and acrylic IOLs than is the case with either PMMA or silicone lenses and they suggest that the interaction would not only mechanically compress the cells, but would impede the diffusion of nutrients to cells on the posterior capsule. Both of these effects could cause the cells to regress and atrophy.
There is now a very worthwhile hypothesis of a direct means of reducing PCO through the design of an IOL which maximises the interaction between the capsule and lens. Hollick et al suggest that as there is initially significant cell growth with acrylic IOLs, this interaction must take several weeks to develop. This hypothesis can only be rigorously tested in molecular and mechanistic terms under long term culture in vitro where not only can cell growth and regression be monitored but routine measurements could also be made of the extent of adhesion between the capsule and IOL. The in vitro models have certainly yielded valuable information concerning the relative efficacy of a range of strategies to prevent or reduce PCO. These have included a comparison of different clinical methodologies in current use,4 12 and suggestions for innovative pharmacological methods for inhibiting PCO.13 14 It is now time for the in vitro experts to elucidate the basic mechanisms of IOL capsule interaction. Such a study may not only give useful information for future IOL design, but intriguingly might also shed some light on the question of why cell division is relatively inhibited and controlled in the whole lens yet so robust and aggressive in the open capsular bag. Both systems are subject to the same external growth factors, but, notably, the internal interactions, both chemical and physical, are quite different within the two systems.