BackgroundThe aims of this study were to determine the 5-year incidence of posterior capsule opacification (PCO) requiring Nd:YAG laser capsulotomy in a representative mixed cohort of cataract patients, to determine risk factors for PCO and to investigate possible association with growth of human lens epithelial cells (HLEC) in vitro.MethodsPieces of the anterior lens capsule and adhering HLEC were obtained at cataract surgery and cultured individually. After one and two weeks respectively, cultured cells were stained with carboxy-fluorescein diacetate succinimidyl ester (CFDA SE), after which image processing software was used to determine the area of the confluent cell layer. The 5-year incidence of Nd:YAG laser capsulotomy in this cohort was determined through medical records and by mail or telephone interviews. For statistic analyses Mann–Whitney U-test, Fisher’s exact test and binary logistic regression were used.ResultsData on treatment/no treatment for PCO was obtained from 270 patients with a median follow-up time of 57 months (range 50–64 months). The three-year cumulative incidence of PCO was 5.2% and the cumulative 5-year incidence was 11.9%. Patients who had undergone Nd:YAG laser capsulotomy were significantly younger (median 71 years) than patients who did not receive treatment for PCO (median 75 years, p = 0.022). Logistic regression demonstrated that apart from younger age, follow-up time and type of intraocular lens (IOL) were associated with risk of PCO, with hydrophilic 1-piece IOLs conferring a higher risk than hydrophobic acrylic 1-piece or 3-piece IOLs (adjusted OR = 9.4, 95% CI 2.5-35.7, p = 0.001). Of the 270 patients from whom information could be retrieved regarding PCO treatment, in vitro cell culture could be established and quantified from 185 patients. No significant difference in cell growth in vitro was shown between patients subsequently requiring/not requiring Nd:YAG laser capsulotomy.ConclusionsThe cumulative 5-year incidence of 11.9% is comparable or slightly higher than reported in other recent studies. The type of IOL was the most important risk factor for PCO in this study, whereas intrinsic proliferative capacity of the individual’s lens epithelial cells seems to be less important for subsequent PCO development.
Aim : Inter-individual differences in intrinsic proliferative capacity of lens epithelial cells may have importance for the risk of developing posterior capsule opacification (PCO) after cataract surgery. The purpose of the present study was to determine growth of human lens epithelial cells (HLEC) in culture and investigate possible associations with clinical characteristics of the donors, such as age, sex, pseudoexfoliation, uveitis and diabetes.Methods : Pieces of lens capsule and adhering lens epithelial cells were obtained through capsulorhexis at cataract surgery. Specimens were cultured in a humidified CO2-incubator using standard culture medium and 5% fetal calf serum for two weeks after which cultured cells were stained with carboxy-fluorescein diacetate succinimidyl ester. Image processing software was used to determine the area of the confluent epithelial cell layer in relation to the size of the original capsule specimen.Results : The increase in area of confluent HLEC showed a negative correlation with diabetes at the first week after surgery. Lower age and female sex showed border-line significant associations with a higher rate of cell proliferation. The presence of pseudoexfoliation in vivo did not significantly affect cell growth in culture postoperatively. Nor did installation of xylocain in the anterior chamber during surgery.Conclusion : Diabetes is associated with lower rate of proliferation of lens epithelial cells in culture. The lack of strong correlations between in vitro growth and known risk factors for PCO in the donors suggest that other factors than the proliferative capacity of the cells per se are important for PCO formation.
ABSTRACT:The hepatic SV40 large T-antigen immortalized human liver epithelial (THLE) cell line and sublines transfected with cytochromes P450 (P450s) are increasingly being used for evaluation of potential drug-induced liver injury. So far, the available information on transporter and enzyme expression in these transfected cell systems is scattered. The purpose of this study was to characterize THLE cell lines with respect to transporter and enzyme expression. The mRNA expression of 96 typical drug absorption, distribution, metabolism and excretion genes, which encode a selection of transporters, phase I and II drugmetabolizing enzymes, and nuclear hormone receptors, was investigated in five THLE cell lines transfected with individual human P450s and in mock-transfected THLE-null cells using real-time polymerase chain reaction. The majority of the analyzed genes was either absent or expressed at low levels in the THLE-null and THLE-P450 cells, apart from housekeeping genes and the individual transfected P450s. Enzyme activity measurements provided confirmatory functional data for CYP2C9 and CYP3A4. Comparison with gene expression in human liver revealed an overall much lower gene expression in the THLE cell lines. The low levels of expression of a broad range of P450 genes in the THLE cell lines highlight the value of studies undertaken with P450-expressing cell lines for investigation of mechanisms of P450 metabolite-mediated hepatotoxicity. However, when attempting to translate between data obtained in THLE cell lines in vitro and functional consequences in vivo, it is important to take account of their limited expression of genes encoding many other drug-metabolizing enzymes and hepatic transporters. IntroductionDrug-induced liver injury (DILI) is a leading cause of clinically significant adverse drug reactions (which include fatal liver failure), withdrawal of licensed drugs, failure to register new drugs, and compound termination due to toxicity during drug development (Kaplowitz, 2005). The causes for DILI are manifold and include both drug-related properties and characteristics of individual patients, which include genotype, underlying disease, comedications, and various other demographic factors (Pachkoria et al., 2007). Human hepatocytes have clear potential value in toxicity evaluations, because they express a broad range of metabolizing enzymes and other desirable differentiated functions (McGinnity et al., 2004;Hewitt et al., 2007). However, because use of hepatocytes to support assessment of toxicity during drug discovery is limited by their relatively high cost and restricted availability, alternative model systems are needed (Kalgutkar and Soglia, 2005). One promising model is the THLE-P450 cell lines, which were developed by transfection of SV40 large T-antigen immortalized human liver epithelial cells with individual human cytochrome P450 (P450) isoforms CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (Pfeifer et al., 1993). The panel of THLE cell lines have been used to explore involvement of indiv...
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