Role of cytokines in the pathogenesis of posterior capsule opacification.

Posterior capsular opacification (PCO) is the most common complication of cataract surgery, occurring in up to 50% of cases, and a recent clinical survey suggested that the incidence is not declining in spite of improvements in surgical technique. At present PCO is treated by YAG capsulotomy, which carries a small risk of sight threatening complications such as cystoid macular oedema or retinal detachment and is expensive, costing the US Medicare programme $250 million in 1993. YAG laser capsulotomy is frequently not available in underdeveloped countries, adding considerably to the problems of treating third world blindness from cataract. The clinical and economic significance of PCO makes it an important public health problem, and in order to prevent it a clear understanding of the pathogenesis is needed. Cataract surgery induces a wound healing response in the lens with cellular proliferation and laying down of extracellular matrix (ECM). PCO results from the proliferation of lens epithelial cells (LEC) remaining in the capsular bag after any type of extracapsular cataract extraction. Visual loss occurs as a result of centripetal migration of LECs associated with fibrosis and wrinkling of the posterior capsule. Histology has shown that there are two areas within the capsular bag where cellular activity leads to the formation of PCO—the cuboidal anterior epithelial cells and the equatorial lens bow cells, which are both derived embryologically from ectoderm at 8 weeks’ gestation. Clinically there are two morphological types of PCO—wrinkling and haze from fibrosis on the capsule and epithelial pearls from regeneration of lens fibres. McDonnell and co-authors, 6 have shown that the anterior epithelial cells in both rabbits and humans initially undergo hyperplasia and, by 4 days after surgery, transform into spindle-shaped myofibroblast cells. This process starts at the cut edge of the anterior capsule and by 1 week a ring of fibrosis forms around the rhexis where it touches the posterior capsule in the aphakic eye. The cells are surrounded by multilaminated basement membrane material composed of proteoglycans and collagen fibrils. The predominant proteoglycans found are dermatan sulphate, chondroitin sulphate, and heparan sulphate, which are thought to determine the thickness of the collagen fibrils. The main types of collagen are I, IV, V, and VI. In rabbits a high proportion of the fibroblast-like cells have 4–6 nm diameter intracytoplasmic filaments which are an isoform of actin, alpha smooth muscle actin (á-SMA). This cytoskeleton gives these cells a retractile property and, owing to their longitudinal orientation, they may cause wrinkling of the posterior capsule which is seen in areas where cells express á-SMA. Kurosaka et al 8 found that in rabbits that had undergone cataract extraction, flattened LECs formed at the edge of the capsulorhexis by the fifth day. These cells expressed á-SMA and were related to areas of the posterior capsule where there was wrinkling. The epithelial cells of the equator are also capable of undergoing fibrous metaplasia. After in the bag intraocular lens (IOL) implantation a fibrous encapsulation occurs around the haptics within the equatorial fornix. The lens bow cells of the equatorial region, however, have a stronger tendency than the anterior epithelial cells towards migration and the formation of epithelial pearls which are characterised by the presence of bladder cells. Bladder cells appear to represent LECs that are trying to form lens fibre cells. They are 0.6–1.0 mm diameter and have a homogeneously granular cytoplasm with either a pyknotic or no nucleus. Immunohistochemistry has shown that these cells do not express á-SMA. In cataractogenesis, these lens bow cells can also migrate along the posterior capsule to form posterior subcapsular cataracts, where some of them assume the histological characteristics of bladder cells.