The Thrombospondin1-TGF-β Pathway and Glaucoma.
Glaucoma is characterized by abnormal remodeling of the extracellular matrix (ECM) in the trabecular meshwork and in the connective tissue beams of the lamina cribrosa (LC) at the optic nerve head (ONH), which is associated with axonal damage. Mechanical strain can stimulate ECM remodeling and increased expression of matricellular proteins. Thrombospondins 1 and 2 are induced by cyclic mechanical strain in the eye in both the trabecular meshwork and in the LC region of the ONH. TGF-betas 1 and 2 are increased in glaucoma and play a role in the pathologic remodeling of the ECM in the eye in glaucoma. In this study, we address the role of thrombospondin1 as a regulator of latent TGF-beta activation and discuss the potential therapeutic use of antagonists of the thrombospondin1-TGF-beta pathway for treatment of glaucoma.
1 Department of Pathology, University of Alabama at Birmingham , Birmingham, Alabama.|2 Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham , Birmingham, Alabama.|3 Department of Ophthalmology, University of Alabama at Birmingham , Birmingham, Alabama.
Joanne E
JE
Murphy-Ullrich
3 Department of Ophthalmology, University of Alabama at Birmingham , Birmingham, Alabama.|4 Department of Biomedical Engineering, University of Alabama at Birmingham , Birmingham, Alabama.
J Crawford
JC
Downs
D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005901:Glaucoma / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000378:metabolism*; D014129:Trabecular Meshwork / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D019700:Thrombospondin 1; D053781:Transforming Growth Factor beta2