Janssen, Andreas and Hoellenriegel, Julia and Fogarasi, Marton and Schrewe, Heinrich and Seeliger, Mathias and Tamm, Ernst and Ohlmann, Andreas and May, Christian Albrecht and Weber, Bernhard H. F. and Stoehr, Heidi (2008) Abnormal vessel formation in the choroid of mice lacking tissue inhibitor of metalloprotease-3. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 49 (7). pp. 2812-2822. ISSN 0146-0404,
Full text not available from this repository. (Request a copy)Abstract
PURPOSE. Tissue inhibitor of metalloprotease (TIMP)-3 is an inhibitor of matrix metalloprotease (MMP) and regulates angiogenesis. In the eye, TIMP3 is tightly associated with Bruch's membrane. In this study, the authors analyzed mice lacking TIMP3 for retinal abnormalities. METHODS. Mice with targeted disruption of the Timp3 gene were generated (Timp3(-/-)) and bred into C57/B16 and CD1 backgrounds. Eyes were analyzed by light and electron microscopy. Vasculature was examined by scanning laser ophthalmoscopy, corrosion casts, and whole mount preparations. MMP activity was assessed by in situ zymography, angiogenic potential was evaluated by tube formation, and aortic ring assays and signaling pathways were studied by immunoblotting. RESULTS. TIMP3-deficient mice develop abnormal vessels with dilated capillaries throughout the choroid. Enhanced MMP activity in the choroid region of Timp3(-/)-eyes was detected when compared with controls. Timp3(-/-)-derived tissue showed an increased angiogenic activity over wild-type, an effect that could specifically be inhibited by recombinant TIMP3. Moreover, the antiangiogenic property of TIMP3 was demonstrated to reside within the C-terminal domain. When VEGFR2 inhibitor was added to Timp3(-/)-aortic explants, endothelial sprout formation was markedly reduced, which provided evidence for an unbalanced VEGF-mediated angiogenesis in Timp3(-/)-animals. Finally, angiogenic signaling pathways are activated in Timp3(-/-)-derived cells. CONCLUSIONS. These findings suggest that the distinct choroidal phenotype in mice lacking TIMP3 may be the result of a local disruption of extracellular matrix and angiogenic homeostasis, and they support an important role of TIMP3 in the regulation of choroidal vascularization.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; SORSBYS FUNDUS DYSTROPHY; METALLOPROTEINASES-3 TIMP3; MATRIX METALLOPROTEINASES; TUMOR-GROWTH; IN-VITRO; ANGIOGENESIS; CHORIOCAPILLARIS; LOCALIZATION; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Oct 2020 10:46 |
| Last Modified: | 28 Oct 2020 10:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30680 |
Actions (login required)
 |
View Item |
