| Decreased caspase-3 activity in human lens epithelium from posterior subcapsular cataracts. | |
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MedLine Citation:
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PMID: 12565805 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Madeleine Andersson; Antovan Honarvar; Johan Sjöstrand; Anne Peterson; Jan-Olof Karlsson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental eye research Volume: 76 ISSN: 0014-4835 ISO Abbreviation: Exp. Eye Res. Publication Date: 2003 Feb |
Date Detail:
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Created Date: 2003-02-04 Completed Date: 2003-03-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370707 Medline TA: Exp Eye Res Country: England |
Other Details:
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Languages: eng Pagination: 175-82 Citation Subset: IM |
Copyright Information:
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Copyright 2003 Elsevier Science Ltd. |
Affiliation:
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Section of Ophthalmology, Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden. madeleine.andersson@oft.gu.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Caspase 3 Caspases / drug effects, metabolism* Cataract / enzymology*, pathology Cell Culture Techniques / methods Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Epithelial Cells / drug effects, enzymology*, pathology Female Humans Lens Capsule, Crystalline / drug effects, enzymology*, pathology Male Staurosporine / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 62996-74-1/Staurosporine; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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