Human Capsular Bags Research Articles

Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts.

Posterior capsule opacification (PCO) is a common complication after cataract surgery. Residual lens epithelial cells (LECs) on the anterior lens capsule, after cataract surgery, migrate to the posterior lens capsule and undergo transdifferentiation into myofibroblast-like cells. Those cells synthesize excessive amounts of extracellular matrix and contribute to fibrosis during PCO. Cellular senescence, a phenomenon that increases with aging, has been implicated in several fibrotic diseases. Here, we have investigated the prevalence of senescent LECs within the lens posterior capsule and the ability of advanced glycation end products (AGEs) in lens capsules to induce senescence, contributing to PCO. Aged lens capsules from pseudophakic human cadaver eyes showed the presence of senescent LECs. In human capsular bags, LECs showed an age-dependent increase in senescence after 28 days of culture. Human LECs cultured on aged lens capsules for 3 days underwent senescence; this effect was not seen in LECs cultured on young lens capsules. Human LECs cultured on an AGE-modified extracellular matrix (ECM-AGEs) showed an AGE-concentration-dependent increase in the expression of senescence markers and reactive oxygen species (ROS) levels. Treatment with a RAGE antagonist and ROS inhibitor reduced the expression of senescence and fibrotic markers. Additionally, conditioned media from ECM-AGEs-treated cells induced the expression of fibrotic markers in naïve LECs. Together, these suggest that AGEs in the capsule induce senescence of LECs, which triggers the mesenchymal transition of neighboring non-senescent LECs and contributes to PCO.

Conditions for modifying intraocular lenses as drug carriers for methotrexate using poly (lactic-co-glycolic acid).

The intraocular lens (IOL) can be used as a slow-release drug carrier in cataract surgery to alleviate posterior capsular opacification (PCO). The following is a systematic development of an IOL using methotrexate and the solvent casting process with poly (lactic-co-glycolic acid) (PLGA) as a carrier polymer. Different solvents for PLGA and methotrexate were tested for dissolution properties and possible damage to the IOL. The required biological concentration of methotrexate was determined in human capsular bags implanted with an IOL. To detect fibrosis, α-SMA, f-actin, and fibronectin were labelled by immunofluorescence staining. Cell proliferation and extracellular matrix contraction were observed in a lens epithelial cell line (FHL-124). Finally, the IOL was designed, and an ocular pharmacokinetic model was used to measure drug release. Solvent mixtures were found to allow coating of the IOL with drug and PLGA without damaging it. PCO in the capsular bag model was inhibited above 1 μM methotrexate (p = 0.02). Proliferation in FHL-124 was significantly reduced above a concentration of 10 nM (p = 0.04) and matrix contraction at 100 nM (p = 0.02). The release profile showed a steady state within therapeutic range. After determination of the required physicochemical manufacturing conditions, a drug releasing IOL was designed. A favourable release profile in an ocular pharmacokinetics model could be shown.

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3.

Posterior capsule opacification (PCO) is a complication after cataract surgery that can disrupt vision. The epithelial to mesenchymal transition (EMT) of lens epithelial cells (LECs) in response to transforming growth factor β2 (TGFβ2) has been considered an obligatory mechanism for PCO. In this study, we tested the efficacy of aspirin in inhibiting the TGFβ2-mediated EMT of human LECs, LECs in human lens capsular bags, and lensectomized mice. In human LECs, the levels of the EMT markers α-smooth muscle actin (α-SMA) and fibronectin were drastically reduced by treatment with 2 mM aspirin. Aspirin also halted the EMT response of TGFβ2 when introduced after EMT initiation. In human capsular bags, treatment with 2 mM aspirin significantly suppressed posterior capsule wrinkling and the expression α-SMA in capsule-adherent LECs. The inhibition of TGFβ2-mediated EMT in human LECs was not dependent on Smad phosphorylation or MAPK and AKT-mediated signaling. We found that aspirin significantly increased the acetylation of K56 and K122 in histone H3 of human LECs. Chromatin immunoprecipitation assays using acetyl-H3K56 or acetyl-H3K122 antibody revealed that aspirin blocked the TGFβ2-induced acetylation of H3K56 and H3K122 at the promoter regions of ACTA2 and COL1A1. After lensectomy in mice, we observed an increase in the proliferation and α-SMA expression of the capsule-adherent LECs, which was ameliorated by aspirin administration through drinking water. Taken together, our results showed that aspirin inhibits TGFβ2-mediated EMT of LECs, possibly from epigenetic down-regulation of EMT-related genes.

Development of a drug-eluting intraocular lens to deliver epidermal growth factor receptor inhibitor gefitinib for posterior capsule opacification prophylaxis.

Different molecular targets, such as the epidermal growth factor receptor, have been identified for the prophylaxis of posterior capsule opacification. This led to the proposal of several drugs, yet drug delivery into the capsular bag remains challenging. The intraocular lens as a drug delivery device would provide a convenient method to allow drug release in the location needed. This is to evaluate the effect of a drug-eluting intraocular lens using an epidermal growth factor receptor inhibitor. Hydrophobic and hydrophilic intraocular lenses were coated with gefitinib using the dip coating technique. The cellular response on the modified intraocular lenses was tested in a human lens epithelial cell line (FHL-124) in an anterior segment model. Furthermore, modified intraocular lenses were implanted into human capsular bags ex vivo. Drug release was determined as well as the biocompatibility on human corneal endothelial cells. Unmodified intraocular lenses served as controls. In addition, immunofluorescence staining with fibronectin as a marker for fibrotic response was conducted. Both coated hydrophilic and hydrophobic intraocular lenses could attenuate the cell growth of FHL-124 cells in the human capsular bag in comparison to the unmodified controls. Furthermore, gefitinib-soaked intraocular lenses showed a constant drug release over the first 10 days. No reduction in cell viability of corneal endothelial cells occurred. A decrease in fibronectin expression under gefitinib treatment could be observed. In vitro epidermal growth factor receptor seems to be a valuable target for the prevention of posterior capsule opacification. The gefitinib-eluting intraocular lens in this study could inhibit cell growth in non-toxic concentrations.

Resveratrol Inhibits Wound Healing and Lens Fibrosis: A Putative Candidate for Posterior Capsule Opacification Prevention.

Posterior capsule opacification (PCO) is a common complication of cataract surgery. In addition to improved surgical methods and IOL designs, it is likely additional agents will be needed to improve patient outcomes. Presently no pharmacological agent is in clinical use to prevent PCO. Here we investigate the putative ability of resveratrol (RESV), a naturally occurring polyphenol, as a therapeutic agent. The human lens epithelial cell line FHL124, a human lens capsular bag model, and central anterior epithelium were used as experimental systems. Standard culture was in 5% fetal calf serum Eagle's minimum essential medium; 10 ng/mL transforming growth factor-β2 (TGFβ2) was used to induce fibrotic changes. A scratch wound assay was used to measure cell migration and the patch assay was used to assess matrix contraction by FHL124 cells. Protein expression was assessed by immunocytochemistry and Western blot and gene expression by quantitative RT-PCR. In capsular bags, cell growth across the posterior lens capsule, capsular wrinkling, and epithelial-to-mesenchymal transition were determined by image analysis. In FHL124 cells, addition of 30 μM RESV significantly impeded cell migration in a wound-healing assay. RESV significantly inhibited TGFβ2-induced expression of the myofibroblast marker alpha-smooth muscle actin (α-SMA) at both the message and protein levels, as well as significantly inhibiting matrix contraction induced by TGFβ2. In human capsular bags, 30 μM RESV significantly inhibited cell growth. TGFβ2-induced α-SMA expression and capsular wrinkling were also significantly inhibited by RESV treatment. RESV significantly suppressed expression of TGFβ2-induced genes associated with fibrotic disease, including matrix metalloproteinase-2 in FHL124 cells, capsular bags, and central anterior epithelium. RESV can counter PCO-related physiological events in two human lens model systems. RESV therefore has the potential to be used as a candidate agent for the prevention of PCO, which in turn could benefit millions of cataract patients.

Inhibition effects of sulforaphane-induced autophagy flux to cell proliferation on ex vivo human capsular bags

Background Sulforaphane (SFN) is an effective chemopreventive agent and can regulate the biological molecular mechanisms to inhibit the overgrowth of cells.Autophagy is a biological process of maintaining cellular internal environment.Understanding the affection of SFN to biological behavior of human lens epithelial cells (LECs) and the association of SFN with autophagy is helpful for the prevention and target treatment of posterior capsule opacification (PCO). Objective This study was to investigate the eradication effeccts of SFN on residual lens cell population in vitro posterior capsule opacification (PCO) model and evaluate the mechanism of SFN-induced cell death. Methods In vitro human capsular bag models were generated from fresh donor eyes by phacoemulsification and were cultured in EMEM containing 2% fetal bovine serum (FBS). Different concentrations of SFN (0, 1, 10 and 100 μmol) were added in the medium for 30 days respectively according to grouping, and the growth of LECs was observed by optical microscope and immunofluorescence technique.FHL124, a human LEC line, was cultured with EMEM containing 5%FBS and divided into 0, 1, 10, 30 and 100 μmol SFN groups.Lactate dehydrogenase (LDH) release rate in the medium was detected to evaluate cell damage/death.The migration of the cells on capsular bags was assessed by scratch test.The ultrastructure and number of autophagosomes were examined under the transmission electron microscope.The expression of LC3 in the cells were detected using Western blot in the presence or absence of autophagy inhibitors. Results The cell coverage rates on the capsular bags were significantly lower in the 10 and 100 μmol/L SFN groups than those in the 0 and 1 μmol/L SFN groups, with a statistically significant difference among the groups (F=48.57, P<0.01). Immunofluorescence showed that the density of F-actin-and Vimentin-positive cells was evidently decreased in the 10 and 100 μmol/L SFN groups compared with 0 and 1 μmol/L SFN groups.The releasing levels of LDH (absorbancy) were 0.19±0.03, 0.39±0.06, 0.56±0.07, 0.68±0.08 and 0.89±0.09 in the 0, 1, 10, 30 and 100 μmol/L SFN groups, respectively, and the releasing level of LDH was gradually increased in the 10 and 100 μmol/L SFN groups in comparison with the 1 μmol/L SFN group (all at P<0.01). With the increase of SFN concentration, the reduction rate of scratched area decreased with the increase of SFN concentration, and the decrease of scratch area was significantly lower than that of adjacent low mass concentration group and the differences were statistically significant (P<0.05). The relative expressions of LC3-Ⅱ protein were 0.423±0.003, 14.543±0.024, 0.668±0.024 and 0.576±0.056 in the blank control group, SFN group, SFN+ 3-MA group and 3-MA group, respectively, and the relative expressions of LC3-Ⅱ protein were significantly lower in the SFN+ 3-MA group and 3-MA group than those in the SFN group (all at P<0.01). The number of autophagosomes was 4.07±0.32, 4.13±0.34, 9.21±0.53 and 21.02±1.34 in the blank control group, and 1, 10, 100 μmol/L SFN groups, and the number of autophagosomes in the 10 and 100 μmol/L SFN groups was significantly higher than that in the blank control group and 1 μmol/L SFN group (all at P<0.01). Conclusions SFN mediates LECs death by promoting autophagy in ex vivo capsular bags, and SFN may be a novel agent of potential chemopreventive and target treatment for PCO. Key words: Lens capsule, crystalline; Isothiocyanates; Thiocyanates/therapeutic use; Cell line; Lens epithelial cells; Models, biological; Autophagy/drug effects; Posterior capsule opacification

Migration of lens epithelial cells and IOL drug soaking

SummaryPurposeTo assess the effect of EGFR Inhibitor Erlotinib and the downstream Inhibitor Erufosin (PI3K) soaked into intraocular lenses (IOLs) on human lensepithelialcell (LEC) proliferation in vitro.MethodsFoldable IOLs were incubated with Erufosin or Erlotinib. Intraocular lenses of the same lot served as uncoated controls. Each IOL was placed into cell cultre containing proliferating human LECs. Cell survival was tested by the XTT‐dye reduction assay 5 days later. Furthermore IOLs were put into the Gotoh anterior chamber model. In addition, soaked IOLs were implanted into the human capsular bags and braught to cell‐culture. The time until full cell‐coverage of the capsular bag was measured.ResultsErufosin (P&lt;0.05) and Erlotinib (P&lt;0.05) coated IOLs attenuated human LEC proliferation in all above described models. For both substances soaked hydrophilic acrylic IOLs were more effective inhibitors of human LEC proliferation than coated hydrophobic acrylic.ConclusionsResults show that both substances are suitable agents for IOL‐soaking without linker molecules. Soaked IOLs can inhibit human LEC proliferation in our models and might become of clinical relevance in future.

MMP2 Activity is Critical for TGFβ2-Induced Matrix Contraction—Implications for Fibrosis

The fibrotic lens disorder posterior capsule opacification (PCO) develops in millions of patients following cataract surgery. PCO characteristics are extensive extracellular matrix (ECM) production and contraction of the posterior lens capsule, resulting in light-scattering ECM modification (wrinkling). The pro-fibrotic cytokine transforming growth factor beta (TGFβ) is central to PCO development. This study aimed to elucidate the role of the ECM modulators matrix metalloproteinases (MMPs) in TGFβ-mediated PCO formation. The human lens epithelial cell-line FHL-124 and human capsular bag models were employed. Gene expression of MMP family members was determined by oligonucleotide microarray and quantitative real-time RT-PCR. MMP2 and MT1-MMP protein levels were analyzed by ELISA and Western blotting, respectively. Matrix contraction was determined using an FHL-124 patch contraction assay; at end-point, cells were stained with Coomassie brilliant blue and area was determined using image analysis software. Cell coverage and wrinkle formation on the posterior capsule were also assessed using human capsular bag models. Active TGFβ2 (10 ng/mL) increased gene and protein levels of MMP2 and MT1-MMP and induced matrix contraction in FHL-124 cells. Specific siRNA inhibition of MT1-MMP did not suppress TGFβ2-induced matrix contraction. Active TGFβ2-mediated contraction was prevented by broad-spectrum MMP inhibitor GM6001 (25 μM), MMP2 siRNA, and MMP2 neutralizing antibody (4 μg/mL). TGFβ2-induced wrinkle formation was attenuated in human capsular bags treated with MMP2 neutralizing antibody (20 μg/mL). MMP2 plays a critical role in TGFβ2-mediated matrix contraction, which appears to be independent of MT1-MMP. MMP2 inhibition provides a novel strategy for the treatment of PCO and potentially other fibrotic disorders.

A Fully Human In Vitro Capsular Bag Model to Permit Intraocular Lens Evaluation

To establish a fully human in vitro culture model with which to test the putative effects of intraocular lens (IOL) designs in preventing posterior capsule opacification (PCO) after cataract surgery. A sham cataract operation was performed to prepare human capsular bags from donor lenses. In one capsular bag of a donor pair, an intraocular lens (PMMA round-edge IOL or acrylic IOL) was implanted while the other capsular bag remained aphakic. Bags were transferred to a Petri dish and secured anterior-face down using entomological pins. Capsular bags were maintained in Eagle's minimum essential medium supplemented with 2% human serum and 10 ng/mL TGF-β to drive growth and matrix contraction. In the absence of an IOL, cells appeared within the central posterior capsule at 4.38 ± 0.26 days, whereas in the presence of a PMMA round-edge IOL or an acrylic IOL they appeared at 8 ± 0.41 days and 11 ± 0.7 days, respectively. Immunocytochemical analysis showed an accumulation of cells at the edge of the acrylic IOL and a less evident accumulation with the PMMA round-edge IOL. Moreover, matrix contraction was more prominent in the absence of an IOL but was still apparent, to a lesser degree, in the presence of a PMMA round-edge IOL. The acrylic IOL greatly suppressed matrix contraction. The authors have developed a fully human in vitro capsular bag system that relates well to clinical observations and permits the testing of novel intraocular lenses.

Prevention of posterior capsule opacification by combination of arsenic trioxide and perfect capsule

Despite recent improvements in IOL design, posterior capsule opacification (PCO) remains a significant clinical problem after cataract surgery. The Perfect Capsule device (Milvella, Ltd., Epping, Australia) permits the introduction and subsequent removal of potentially toxic agents into the closed capsular bag. The present purpose was to detect the effectiveness of arsenic trioxide (As2O3) to cultured human lens cells and cells within the human capsular bag. All experiments were carried out with 2 minutes exposure to As2O3. Effect of As2O3 on FHL124 cells growth was tested by MTT. Changes in cell calcium levels induced by high concentration of As2O3 were measured by real-time fluorometric single-cell digital imaging techniques after Fura-2 incorporation. In vitro human capsular bags were also tested after a sham surgery was performed using the Perfect Capsule device to form a closed system. As2O3 (10, 30, 100, 300, 1000 µmol/L) were used with donor match-pairs treated with medium alone.(n = 3 in all cases).On-going observations were by phase-contrast microscopy. Cellular architecture was examined by fluorescence cytochemistry. As2O3 of 100 µmol/L and above inhibited the growth of FHL 124 cells in a dose-dependent manner with 2 minutes exposure (t = 5.217, P < 0.01, IC(50) is 130 µmol/L) As2O3 depleted the calcium store and consequently lead to a loss of calcium signaling.Moreover, 1 × 10(4) µmol/L As2O3 had a moderate effect on the calcium influx pathway, inhibition on the amplitude and rapidity is (43.24 ± 2.98)% (t = 3.134, P < 0.01) and (46.27 ± 6.01)% (t = 3.521, P < 0.01), respectively. No cell left in the vitro human capsular bags after being treated with 1 × 10(4) µmol/L As2O3. As2O3 can eliminate the human lens epithelium cells remained in the capsular bag in cataract surgery, which may help to prevent PCO. The application of As2O3 to cells within the capsular bag for a 2 minute window using the Perfect Capsule system predicts this compound will have therapeutic benefit to humans in vivo.

Promotion of ER stress: a potential therapeutic approach for PCO

Abstract Purpose Posterior Capsule Opacification (PCO) remains a significant clinical problem following cataract surgery. Endoplasmic Reticulum (ER) stress has been shown to play a critical role in cell death and apoptosis. The aim of this study was to determine the relative effectiveness of ER stressors, thapsigargin (Tg) and arsenic trioxide (As2O3) on induction of cell death in human capsular bags. Methods FHL124 cell survival was assessed by Coomassie blue staining after 4 days. Induction of ER stress genes was detected using real‐time PCR and apoptosis assessed using the TUNEL assay. Human capsular bags were prepared from donor eyes and sealed with the Perfect Capsule device. The agents were again introduced to the bags for a 2 minute period prior to perfusion with EMEM alone. The bags were maintained in EMEM for 28 days and phase images were acquired throughout. Results Tg and As2O3 application to FHL124 cells induced significant up‐regulation of ER stress genes Bip, EIF2α, IRE1 and ATF6. FHL124 cells exposed for 2 minutes to both Tg and As2O3 for 4 days demonstrated reduced cell survival in a dose‐dependent manner. Moreover, TUNEL assay data showed that both Tg and As2O3 could induce FHL124 cell death by apoptosis. Application of the 100uM Tg and 100mM As2O3 to capsular bags for a 2 minute period using the perfect capsule system resulted in a total loss of viable cells following the 4 week culture period. Conclusion Thapsigargin and arsenic trioxide induce an ER stress in human lens epithelial cells, which is associated with a reduced cell survival and promotion of apoptosis. Using the perfect capsule system, a 2 minute exposure of either agent successfully killed all cells within the capsular bag and thus predicts putative therapeutic benefit in vivo.

Calcium signalling can be bad for you: thapsigargin and PCO prevention

Abstract Purpose: Posterior capsule opacification (PCO) remains a significant clinical problem after cataract surgery. The Perfect Capsule device (Milvella, Ltd) permits the introduction and subsequent removal of potentially toxic agents into the closed capsular bag. The present study aimed to determine the influence of thapsigargin (Tg) exposure on lens cell viability. Methods: FHL124 cells were routinely cultured in Eagle’s minimum essential medium (EMEM). DNA and protein synthesis rates were quantified by measuring the incorporation of 3H‐thymidine and 35S‐methionine. Longer‐term growth was assessed by quantifying the increase in area over time of a circular patch of seeded cells. Human capsular bags were prepared from donor eyes and sealed with the Perfect Capsule device. 100uM Tg was introduced for 2 minutes. The bags were then perfused with EMEM and an IOL inserted before the bags were dissected and pinned to the base of plastic culture dishes and maintained in EMEM for 28 days. Results: Continuous exposure of &gt;100 nM Tg to FHL124 cells for 24 hours significantly inhibited both protein and DNA synthesis. A 2 minute exposure of Tg resulted in a complete loss of viable cells following 4 days of culture. A 2 minute application of 100uM Tg to the capsular bag using the perfect capsule system did not immediately eliminate the residual lens cell population, however, by 4 weeks there were no surviving cells in Tg treated bags while a confluent cover of the posterior capsule was observed in controls. Conclusions: Thapsigargin inhibits cell proliferation and protein synthesis resulting in decreased survival rates. Application of thapsigargin at the time of cataract surgery for a 2 minute period using the Perfect Capsule system provides a promising means of preventing PCO.

Arsenic trioxide initiates ER stress responses, perturbs calcium signalling and promotes apoptosis in human lens epithelial cells

Identification of novel agents to eradicate the residual lens cell population following cataract surgery provides one mode of preventing PCO formation. The present study investigated the biological mechanism of As 2O 3 cytotoxicity in a human lens cell line and capsular bag system. FHL 124 cell survival was assessed by quantification of total protein content, a cell population measure. Gene changes were detected by Real-time PCR; apoptosis by TUNEL assays. Intracellular calcium was measured by real-time fluorimetric single-cell digital imaging techniques after Fura-2 incorporation. In vitro human capsular bags were generated from donor eyes, which involved sham cataract surgery then use of the Perfect Capsule device to form a closed system to deliver As 2O 3 for 2 min. On-going observations were by phase-contrast microscopy. Cellular architecture was examined by fluorescence immunocytochemistry. FHL 124 cells demonstrated a dose-dependent sensitivity to As 2O 3 exposure. A 2 min exposure of As 2O 3 to cells within the capsular bag, using the perfect capsule system, resulted in total cell death when used at 100 mM. As 2O 3 provoked an ER stress response identified through an upregulation of known genes. As 2O 3 depleted the calcium store and consequently lead to reduced calcium signalling. As 2O 3 increased rates of apoptosis. Arsenic trioxide provokes ER stress that leads to down-regulation of calcium signalling resulting in apoptosis. The application of As 2O 3 to cells within the capsular bag for a 2 min window using the Perfect Capsule system predicts putative therapeutic benefit in vivo.

Lens Cell Survival after Exposure to Stress in the Closed Capsular Bag

Despite recent improvements in IOL design posterior capsule opacification (PCO) remains a significant clinical problem after cataract surgery. The Perfect Capsule device (Milvella, Ltd., Epping, Australia) permits the introduction and subsequent removal of potentially toxic agents into the closed capsular bag. The present purpose was to compare the relative effectiveness of exposing cells within the human capsular bag with a range of stresses with clinical potential and to compare the response to the same agents when applied to rabbit capsular bags and to cultured human lens cells. Human capsular bags were prepared from donor eyes and sealed with the Perfect Capsule device. Distilled water, 3 M NaCl, 250 microg/mL, 25 mg/mL 5-fluorouracil and 100 microM thapsigargin (Tg) were introduced for 2 minutes. The bags were then perfused with Eagle's minimum essential medium (EMEM) and an IOL inserted before the bags were dissected and pinned to the base of plastic culture dishes. The bags were maintained in EMEM for 28 days and phase images were acquired throughout. Rabbit eyes were prepared and cultured in a similar manner, although tests were limited to 5-FU (25 mg/mL) and Tg (30-300 microM). FHL124 cells were cultured on plastic (EMEM supplemented with 5% FCS), and serum was removed for 24 hours before exposure to the same agents as human bags. Cell survival was assessed by quantifying Coomassie blue staining after 4 days. Initially, NaCl induced by far the most obvious signs of cell death, especially of anterior cells, followed by 5-FU>water>Tg. However, by 2 weeks, cell death became more apparent in the Tg-exposed bags, and, at the end of 4 weeks, there were no cells surviving. Cells on the posterior capsule were confluent in water-exposed bags (similar to unexposed controls), whereas after NaCl exposure, coverage was incomplete but greater than after 5-FU. In the rabbit bags, exposure to 25 mg/mL 5-FU totally eliminated cells, but 100 microM Tg was ineffective. At the end of a 4-day culture of FHL124 cells exposed for 2 minutes to NaCl, 5-FU or Tg, there were no cells surviving, whereas there was 50% cell survival compared with control cells after water treatment. Tissue-cultured human lens cells are much more sensitive to short-term hyperosmotic than hyposmotic stress, with a rapid onset of cell death of cultured cells exposed to 3 M NaCl. This finding was confirmed in human capsular bags although adherent fibers appear to offer additional protection to 5-FU which can be overcome by the very hydrophobic Tg. The application of the Perfect Capsule system in concert with thapsigargin provides a promising means of preventing PCO.

Evaluation of a human capsular bag model for secondary cataract determination after intraocular lens implantation

To investigate the effect of different intraocular lenses (IOLs) on lens epithelial cells (LECs) and on human capsular bags in vitro and to evaluate the transferability of this model to clinical situations. Sham cataract surgery, including IOL-into-the-bag implantation, was performed on 38 donor eyes after removal of the cornea. The capsular bag including the IOL was removed, pinned on a culture dish, covered with medium, and incubated. Two different IOLs were compared per pair of donor eyes. In each pair of donor eyes, the two different IOLs to be compared were implanted individually into capsular bags. The time required for complete coverage of the posterior capsule by a confluent monolayer of LECs was documented. The following IOLs were compared: three-piece acrylic IOLs of different sizes and single-piece polymethylmethacrylate (PMMA) versus acrylic IOLs. A complete monolayer of LECs on the posterior capsule was observed to form at times varying from 8 days (PMMA IOLs) to more than 60 days (three-piece hydrophobic acrylic IOLs). A significant difference between PMMA IOLs and hydrophobic acrylic IOLs was found. The human capsular bag model employed allows short-term evaluation of secondary cataract formation for different IOLs. This model's correlation with clinical results is good.

Morphologic compatibility of intraocular lens haptics and the lens capsule

Purpose: To evaluate the mechanical relationship between the intraocular lens (IOL) haptic and the capsular bag by quantitatively analyzing the fit of the haptic with the capsule equator and the capsular bag deformity induced by the implanted lens haptics.Setting: Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Japan.Methods: Following implantation of a poly(methyl methacrylate) (PMMA) ring in three excised human capsular bags with continuous curvilinear capsulorhexis (CCC), IOLs with different overall lengths or haptic designs were implanted in the bags and photographed. The straight length of the area of contact between the haptic and the capsule equator on the photographs was measured to provide a quantitative index of in-the-bag fixation and the length from the external margin of the PMMA ring to the external margin of the loop along the maximal diameter of the capsular bag, to indicate the quantitative degree of capsular deformity induced by an IOL.Results: An IOL with modified-C loops produced better fit along the capsule equator and less deformity than an IOL with modified-J loops, and an IOL with an overall length of 12.0 or 12.5 mm produced a sufficiently good fit and less distortion of the capsular bag than an IOL with an overall length over 13.0 mm.Conclusion: An IOL with modified-C loops and an overall length of 12.0 or 12.5 mm is adequate for in-the-bag implantation following CCC.