Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With ageing, accumulation of modified proteins occur in the lens, forming light scattering aggregates. The multicatalytic proteinase complex, or proteasome, is known to be the major system for removal of damaged proteins in many tissues. In this study we attempted to compare levels of proteasome activity in human lens epithelium from clear vs. cataractous lenses. Normal lenses were obtained from eye donors in a cornea bank and samples from cataractous lenses were obtained from an eye clinic during cataract surgery. Proteolytic activity was quantified using the synthetic peptide substrate N-Succ-Leu-Leu-Val-Tyr-AMC, a substrate often used to measure the chymotrypsin-like activity of the proteasome. Addition of 100 micron lactacystin, a proteasome specific inhibitor, totally inhibited proteolysis, certifying the specificity of the assay. Hydrolysis was detected over time as the appearance of the flourogenic cleavage product and correlated to the area of the epithelium-capsule specimens. Proteolytic cleavage of N-Succ-Leu-Leu-Val-Tyr-AMC by the proteasome was higher in lens epithelium from clear donor lenses as compared to samples from cataractous lenses. Median activity in the latter was only 19% of that in the former, a highly significant difference. There was no difference in activity of the proteasome when looking at cortical vs. non-cortical cataract, nor was there any difference between genders. Regression analysis did not reveal any age-dependent relationship, either in the clear group or in the cataractous group. This work is the first to show differences in proteasome activity between clear and cataractous lenses.
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PMID:Proteolytic cleavage of N-Succ-Leu-Leu-Val-Tyr-AMC by the proteasome in lens epithelium from clear and cataractous human lenses. 973 89

The proteasome is a large protease complex that is thought to be responsible for proteolytic removal of damaged proteins. We have previously shown that the level of proteolytic activity due to the proteasome is lower in lens epithelium from human cataractous lenses compared to the activity in epithelium from clear donor lenses. This study aimed to characterize the three main peptidase activities of the proteasome in human lens epithelium with respect to kinetic properties and sensitivity to heat and oxidation. Human lens epithelia were obtained from cataract surgery and analysis performed on pools of epithelial cell cytoplasm. Using the fluorogenic peptide substrates Suc-Leu-Leu-Val-Tyr-AMC (LLVY), Boc-Val-Gly-Arg-AMC (VGR) and Z-Leu-Leu-Glu-betaNA (LLE), Km-values of 56, 678 and 108 micrometers were obtained. All peptidase activities were inhibited by lactacystin, a specific proteasome inhibitor, but at very different rates; with LLVY-hydrolysing activity being the most sensitive (Ki50%=0.15 micrometers). Thermostability was investigated by performing the proteolytic assay at 20 degrees, 37 degrees and 53 degrees C. The trypsin-like activity, as measured by VGR, was completely stable at 53 degrees C for at least 24 hr whereas hydrolysis of LLVY and LLE declined after a few hours at 37 degrees C. Oxidative inhibition was induced by incubation of the samples in 0.5 m m H2O2for 1 or 24 hr. One hour exposure to H2O2caused moderate inhibition of all peptidase activities. The activity could be partially restored by adding 1 m m dithiotreitol, indicating the dependency on intact SH-groups. After 24 hr, peptidase activities were decreased to 25% (LLVY), 73% (VGR) and 44% (LLE) of corresponding control. This inhibition was irreversible for VGR and LLE, but could be partly prevented by the presence of heat shock protein 90 (LLVY and VGR) or alpha-crystallin (LLVY). These data show that the peptidase activities of the human lens proteasome can be modulated by metabolites, such as reactive oxygen species, and by endogenous proteins such as alpha-crystallin and heat shock protein 90.
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PMID:Differential inhibition of three peptidase activities of the proteasome in human lens epithelium by heat and oxidation. 1037 57

Apoptosis has been implied in normal lens development in the embryo as well as in lens fibre differentiation. It has also been suggested to play a role in non-congenital cataract and in the formation of posterior subcapsular opacification, but data on the presence of apoptosis in human lens epithelium from cataractous lenses are scarce and conflicting. The present study aimed to investigate apoptosis in lens epithelium from patients undergoing cataract surgery. The amount of apoptosis detected was correlated to age, gender, type of cataract, medications and disease. Moreover, the ability of human lens epithelial cells in culture to respond to the apoptosis-inducing agent staurosporin by activation of caspase-3 was investigated. Human lens capsulotomy specimens were collected immediately after surgery, frozen and later analysed with respect to caspase-3 activity, using the fluorogenic substrate Ac-DEVD-AMC. Generally, the activity of caspase-3 detected in this manner was very low and in 23% of the specimens it was non-detectable. However, there were differences in caspase activity between lens epithelial cells from different types of cataract, where samples from lenses with posterior subcapsular cataract exhibited significantly lower caspase-3 activity than lenses with a clear subcapsular zone. Age, gender or medications did not show any correlation with caspase activity but human capsulotomy specimens from diabetic patients exhibited significantly lower caspase-3 activity. Staurosporin caused a concentration-dependent increase in caspase activity in cultured human lens epithelial cells and the amount of apoptotic nuclei was also increased as viewed by staining with Hoechst 33342, showing chromatin condensation and nuclear fragmentation. Similar results were obtained when fresh human lens capsulotomy specimens were exposed to 1000 nM staurosporin for 24 hr. To conclude, the present data indicate that human lens epithelial cells have the ability to respond to apoptosis-inducing agents with caspase-3 dependent apoptosis, and that even though the general level of apoptosis in human lens epithelium in vivo is low, there are differences in caspase-3 activity levels in lenses with or without posterior subcapsular cataract. The latter finding supports previous studies indicating that this type of cataract may result from defective differentiation, in which apoptosis may play an important role.
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PMID:Decreased caspase-3 activity in human lens epithelium from posterior subcapsular cataracts. 1256 5

The purpose of the study was to report the long-term outcome of unilateral implantation of a multifocal intraocular lens (IOL) in a pediatric cataract. This study was carried out at Tertiary Academic Ophthalmology Department, AMC, Amsterdam. This is a case report study of a 7-year-old child with a unilateral irradiation cataract, in whom an apodized diffractive multifocal IOL (SN6D3, Alcon) was implanted at the time of cataract surgery. During the follow-up period, visual acuity was preserved at logMAR -0.1; the child did not develop amblyopia. Binocular single vision was established. Few glistenings were seen on the IOL. The non-operated eye developed more myopia during the follow-up period than the multifocally implanted eye. Straylight was increased to log(s) 1.83. Patient and parents satisfaction were high. In selected cases, unilateral implantation of apodized diffractive multifocal IOLs leads to good long-term results in terms of visual acuity and patient satisfaction. No untoward effects were seen, including few glistenings on the IOL. Straylight is increased, but subjectively not disturbing.
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PMID:Seven-year follow-up of unilateral multifocal pseudophakia in a child. 2709 Aug 2