Abnormal vessel formation in the choroid of mice lacking tissue inhibitor of metalloprotease-3

Investigative Ophthalmology & Visual Science
Andreas JanssenHeidi Stöhr

Abstract

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. Mice with targeted disruption of the Timp3 gene were generated (Timp3(-/-)) and bred into C57/Bl6 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. 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, endo...Continue Reading

Citations

May 30, 2009·The Journal of Biological Chemistry·Jian Hua QiBela Anand-Apte
Jan 10, 2013·Investigative Ophthalmology & Visual Science·Nina Jasmin HewingCarl Peter Blobel
Oct 29, 2008·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Anne M MacgregorMarc K Halushka
Mar 3, 2012·Journal of the American Society of Nephrology : JASN·Claudia SchrimpfJeremy S Duffield
May 27, 2014·Progress in Retinal and Eye Research·Susanne RoosingFrans P M Cremers
Dec 10, 2015·Ocular Immunology and Inflammation·Yosuke HaradaDebra A Goldstein
Feb 27, 2010·Critical Reviews in Biochemistry and Molecular Biology·Monika Gooz
Jan 2, 2010·Progress in Retinal and Eye Research·Debora L Nickla, Josh Wallman
Sep 4, 2009·Journal of Cellular and Molecular Medicine·R F Nicosia
Dec 10, 2015·Annals of Neurology·Carmen CaponeAnne Joutel
Feb 17, 2009·Developmental Cell·M Luisa Iruela-Arispe, George E Davis
Oct 3, 2009·Trends in Endocrinology and Metabolism : TEM·Maryam AhmadianHei Sook Sul
Feb 27, 2017·Calcified Tissue International·Brendyn MillerAlessandra Carriero
Jun 22, 2019·Annual Review of Vision Science·Ileana SotoGareth R Howell
Jul 6, 2020·International Ophthalmology·Francisco de Asís Bartol-PuyalLuis Pablo
Oct 31, 2020·International Journal of Molecular Sciences·Alexandru TirpeIoana Berindan-Neagoe
Jul 20, 2021·Progress in Retinal and Eye Research·J BrinksC J F Boon

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.