A. D. Dick
Tissue inhibitor of metalloproteinase-3 differentially binds to components of Bruch's membrane
Dick, A. D.; Majid, Mohammed A.; Smith, Valerie A.; Matthews, Fiona; Newby, A. C.
Authors
Mohammed A. Majid
Valerie A. Smith
Fiona Lawrence Fiona.Lawrence@uwe.ac.uk
Director of Business Development & Partnerships
A. C. Newby
Abstract
Background: Sorsby's fundus dystrophy (SFD) is caused by mutations in tissue inhibitor of metalloproteinase (TIMP)-3 and, with the exception of early onset, is similar to age-related macular degeneration. The pathological features of this condition relate to the accumulation of TIMP-3 in Bruch's membrane. Aims: To compare the extracellular membrane-binding characteristics of wild-type and four SFD-mutant TIMP-3s. Methods: COS-7 cells were transfected with wild-type, Ser-181, Gly-167, Ser-156 and Tyr-168 SFD-mutant TIMP-3 cDNA. The TIMP-3 proteins subsequently synthesised were harvested, analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, semiquantified by EUSA and used in binding assays on the basis of the retention of the wild-type and SFD-mutant TIMP-3 proteins by components of Bruch's membrane. Results: SFD-mutant TIMP-3s could not be distinguished from wild-type TIMP-3 by the extents to which they aggregated or adhered to type-i collagen, type-IV collagen, fibronectin, laminin, elastin, chondroitin sulphates A, B and C, and heparin sulphate. Of these macromolecules, the wild-type and SFD-mutant TIMP-3s exhibited greatest affinity for elastin and laminin. Conclusion: The similarity in the physical and extracellular membrane-binding characteristics of wild-type and SFD-mutant TIMP-3s indicates that these properties are not responsible for the difference in timing of onset of SFD and age-related macular degeneration.
Journal Article Type | Article |
---|---|
Publication Date | Oct 1, 2006 |
Journal | British Journal of Ophthalmology |
Print ISSN | 0007-1161 |
Electronic ISSN | 1468-2079 |
Publisher | BMJ Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 90 |
Issue | 10 |
Pages | 1310-1315 |
DOI | https://doi.org/10.1136/bjo.2006.097246 |
Keywords | tissue inhibitor, Bruch's membrane |
Public URL | https://uwe-repository.worktribe.com/output/1036315 |
Publisher URL | http://dx.doi.org/10.1136/bjo.2006.097246 |
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