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Background: We report on three patients who showed a rare complication, centripetal membranous proliferation from the posterior capsulotomy edge onto the posterior surface of an intraocular lens (IOL), 3 to 6 months after neodymium:YAG (Nd:YAG) capsulotomy., Cases: These three patients had juvenile rheumatoid arthritis, retinitis pigmentosa, and sarcoidosis, respectively, prior to cataract surgery., Observations: Elschnig's pearls developed in the eyes of all three patients after cataract surgery, and were treated by Nd:YAG laser. However, membranous proliferation continued, and Nd:YAG laser treatment was required a second time to disrupt the proliferating fibrous membrane and achieve resolution of the patients' symptoms., Conclusions: Common factors in our cases and cases in the literature were that the IOLs were biconvex and made of polymethyl methacrylate. Ophthalmologists should be aware that after cataract surgery, lens epithelial cells can proliferate onto any surface that provides adequate protein nourishment.

Purpose: To evaluate the inhibitory effect of a sharp intraocular lens (IOL) optic edge, a sharp capsule bend, and contact pressure between the optic edge and posterior capsule on lens epithelial cell (LEC) migration., Setting: Department of Ophthalmology, Kyorin University, Tokyo, Japan., Methods: This in vitro laboratory study evaluated a tumble-polished convex-plano IOL (CP group), an AcrySof IOL (Alcon) with a sharp edge (AS group), a new IOL with a round ridge (RR group), and a new IOL with a sharp ridge (SR group). The 2 new IOLs have high ridges and high angled loops that create firm contact between the ridge and posterior capsule. After sham cataract surgery, an IOL and a capsular tension ring (CTR) were implanted in the capsular bag of rabbit eyes. The extracted capsular bags containing the CTR and IOL were cultured. The inhibitory effect of each IOL on cell migration was analyzed. Furthermore, LEC migration on the posterior capsule was compared in culture between capsules having a sharp right angle and those with gradually curving bends., Results: The inhibitory effect on cell migration was statistically greatest in the SR group followed by the RR, AS, and CP groups. A sharp capsule bend did not inhibit cell migration., Conclusions: The results suggest that inhibition of cell migration at the optic edge is regulated by the degree of contact pressure between the optic edge and posterior capsule. A sharp capsule bend might indicate strong contact but does not in itself inhibit cell migration.

Purpose: Lens epithelial cells transdifferentiate to myofibroblasts during the formation of anterior subcapsular cataracts and secondary cataracts. One of the defining characteristics of myofibroblasts is the expression of alpha-smooth muscle actin (alpha-SMA). This study investigated some of the factors that influence alpha-SMA expression in lens epithelial cells., Methods: Bovine, rabbit, and human lens epithelial explants or cells were cultured with or without serum. Immunohistochemistry and immunoblotting were used to detect and quantitate alpha-SMA expression., Results: Cells from all species studied expressed alpha-SMA in primary explant culture with or without serum. Immunostaining for alpha-SMA first appeared in a diffuse granular pattern, then accumulated at the cell cortex, and eventually was detected along stress fibers. When lens epithelial cells migrated onto cell-free regions of the capsule or were transferred to a plastic culture dish, alpha-SMA expression increased significantly. Expression of alpha-SMA positively correlated with cell size and cell migration., Conclusions: Expression of alpha-SMA is a common feature of cultured mammalian lens epithelial cells. Because alpha-SMA expression occurred without the addition of exogenous factors, the fibrosis seen in anterior subcapsular cataracts or secondary cataracts may reflect the intrinsic properties of lens epithelial cells. Interaction between lens epithelial cells and their substratum appears to be an important regulator of myofibroblast formation. Understanding the factors that regulate alpha-SMA expression in lens epithelial cells could lead to the development of methods for preventing secondary cataracts and anterior subcapsular cataracts.

We evaluated the effect of specimens of pre- and postoperative aqueous humor on the contraction of collagen gels, and the effect of transforming growth factor-beta(2) (TGF-beta(2)) in postoperative aqueous humor. Rabbit aqueous humor was collected preoperatively and on postoperative day 7. Bovine lens epithelial cells (LECs) were cultured in collagen gel in F-12 nutrient mixture supplemented with 5% fetal bovine serum that contained 10% aqueous humor obtained under various conditions. Gel area was determined on day 4. Gels cultured with the medium that contained phosphate-buffered saline showed a statistically significant contraction after 4 days. Aqueous humor from aphakic or pseudophakic eyes significantly increased contraction, with both specimens having a similar effect. Approximately 60% of the contractile effect of the postoperative aqueous humor was neutralized by anti-TGF-beta(2) antibody. However, the promoting effect of the aqueous humor sampled postoperatively was less than that sampled preoperatively. Although the aqueous humor obtained postoperatively increased the contractility of the LECs, with the level of TGF-beta(2) apparently responsible for much of its effect, the effect was less than that observed in the aqueous humor obtained preoperatively., (Copyright 2000 S. Karger AG, Basel)

Purpose: To determine whether apoptosis or necrosis of lens epithelial cells occurs after lens extraction., Methods: Lens extraction was performed on 24 rabbit eyes. The authors then performed terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and transmission electron microscopy on the eyes 1 to 10 days after surgery., Results: The postoperative lens was demarcated into three regions by the adhesion between the incised edge of the anterior capsule and the posterior capsule: the adhesive region, the intracapsular region, and the central portion of the posterior capsule. By day 2, TUNEL-positive cells with morphologic characteristics of necrosis were detected in the intracapsular region. Beginning on day 5, TUNEL-positive cells with morphologic characteristics of apoptosis and necrosis were detected in the adhesive region. Apoptotic cell death in this region was detected among the myofibroblast-like cells. Lens epithelial cells that had extended onto the central portion of the posterior capsule began to diminish on day 8 or 9, some of them morphologically demonstrating necrotic changes., Conclusions: Apoptosis of lens epithelial cells occurs in the process of wound healing and reepithelialization after lens extraction, leading to secondary cataract. If the induction of apoptosis is better understood, protocols might be developed that could prevent reepithelialization through apoptosis, thus delaying or preventing secondary cataracts.

Purpose: To find the conditions that prevent posterior capsule opacification through in vitro analysis of the relationship between intraocular lens (IOL) optic configuration and lens epithelial cell (LEC) migration., Setting: Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Japan., Methods: In a preliminary experiment, we measured the size of the capsular bag of rabbits at 8, 16, 20, and 26 weeks of age. The size of a 20-week-old capsular bag was the same size as the capsular bag in senescent Japanese eyes. We isolated the capsular bags in 20- and 8-week-old rabbits. The bags along with a biconvex (BC), convex-plano (CP), or no IOL (C) were cultured, and the eyes were divided into one of six groups (8W-C, 8W-BC, 8W-CP, 20W-C, 20W-BC and 20W-CP), each including six specimens., Results: Two specimens in the 8W-CP group completely blocked LEC migration at the optic edge. All specimens in the 20W-CP group and one in the 20W-BC group showed cell aggregation along the optic edge. None of the other specimens in the BC and C groups blocked migration or showed cell aggregation., Conclusions: In the rabbit-model study, the convex-plano lens was superior to the biconvex lens in inhibiting migration of LECs. A firm contact between the IOL and the posterior capsule blocked the migration.

Purpose: To investigate lens epithelial cell (LEC) proliferation on the posterior capsule in an in vitro model., Setting: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan., Methods: We cultured the cells remaining on the postoperative capsular bag and expanded the capsule with an open poly(methyl methacrylate) ring to simulate actual postoperative conditions. Using human and rabbit cadaver eyes, we monitored the migration and proliferation of LECs onto the postoperative capsular bag by time-lapse videomicroscopy., Results: The remaining viable cells migrated onto the posterior capsule through the equator and directly from the anterior capsule. The cells typically proliferated in a monolayer because of contact inhibition of cell movement and division, but they proliferated in a multilayer at some regions where nonviable cells had accumulated and there were capsular folds., Conclusion: A means to block both routes of cell expansion must be developed to prevent LEC migration onto the posterior capsule.

Purpose: To determine whether basic fibroblast growth factor (bFGF) and transforming growth factor-beta 2 (TGF-beta 2) influence the contractile activity and the expression of alpha-smooth muscle actin (alpha-SMA) in bovine lens epithelial cells (LECs). To examine whether modulation of contractile activity by these growth factors depends on changes of alpha-SMA expression., Methods: Bovine LECs were cultured in collagen gel in MED 5 medium (F-12 nutrient mixture supplemented with 5% fetal bovine serum) with or without bFGF (1 to 100 ng/ml) or TGF-beta 2 (0.01 to 10 ng/ml). To evaluate collagen gel contraction, the longest and shortest diameters of the gels were measured daily for 7 days, and the area was determined. Detection of alpha-SMA in the gels was performed immunohistochemically using a mouse monoclonal antibody against alpha-SMA. The percentage of alpha-SMA-positive cells to the total number of cells was determined., Results: Control gels cultured with MED 5 medium alone contracted to 15.8% +/- 3.4% of their original area after 7 days. TGF-beta 2 significantly increased this contraction in a dose-dependent manner, whereas bFGF significantly decreased it. Approximately 30% of cells in the control gels were alpha-SMA positive. TGF-beta 2 significantly increased the alpha-SMA positivity dose dependently, whereas bFGF significantly decreased it. The percent positivity for alpha-SMA and the gel area showed a significant negative correlation., Conclusions: TGF-beta 2 increased collagen gel contraction and alpha-SMA expression in bovine LECs, whereas bFGF decreased these parameters. Because collagen gel contraction was correlated with alpha-SMA expression, the modulation of LEC contractile activity by growth factors may be related to an effect on alpha-SMA.

We performed slitlamp microscopy and specular microscopy in 15 patients who had cataract surgery to determine the clinical course of postoperative membranous proliferation from the anterior capsulotomy margin onto the intraocular lens optic. Membranous proliferation observed in 11 of the 15 eyes eventually resolved in 10 eyes. We speculate that lens epithelial cells were the origin of the membrane.

Purpose: To determine whether transforming growth factor-beta 2 (TGF-beta 2) in human aqueous humor inhibits the proliferation of lens epithelial cells., Methods: Bovine lens epithelial cells (BLECs) obtained from the central zone of the anterior capsule were cultured in complete medium (F-12 nutrient mixture supplemented with 5% fetal bovine serum). Human aqueous humor was obtained from 11 patients during cataract surgery. Medium was removed and replaced with medium containing various concentrations of porcine platelet-derived TGF-beta 2 or 10% human aqueous humor, with or without anti-TGF-beta 2 neutralizing antibody. The number of cells was counted at 96 hours., Results: Porcine platelet-derived TGF-beta 2 inhibited BLEC proliferation in a dose-dependent manner. Anti-TGF-beta 2 antibody blocked the inhibitory effect of TGF-beta 2 on BLEC proliferation. The 10% human aqueous humor stimulated the proliferation of BLECs. Addition of anti-TGF-beta 2 antibody to the 10% human aqueous humor significantly enhanced this stimulatory effect on BLEC proliferation., Conclusions: TGF-beta 2 in human aqueous humor inhibits the proliferation of lens epithelial cells in vitro.