The Role of TGF-β2 and Bone Morphogenetic Proteins in the Trabecular Meshwork and Glaucoma
| Autor: | Tasneem Putliwala Sharma, Abbot F. Clark, Robert J. Wordinger |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Intraocular pressure Pathology genetic structures Glaucoma Bone morphogenetic protein Aqueous Humor Extracellular matrix Transforming Growth Factor beta2 Risk Factors Trabecular Meshwork Fibrosis Internal medicine medicine Animals Humans Pharmacology (medical) Review Articles Intraocular Pressure Pharmacology business.industry medicine.disease eye diseases Extracellular Matrix Ophthalmology Endocrinology medicine.anatomical_structure Bone Morphogenetic Proteins sense organs Trabecular meshwork Signal transduction business Glaucoma Open-Angle Signal Transduction Transforming growth factor |
| Zdroj: | Journal of Ocular Pharmacology and Therapeutics. 30:154-162 |
| ISSN: | 1557-7732 1080-7683 |
| DOI: | 10.1089/jop.2013.0220 |
| Popis: | Primary open-angle glaucoma (POAG) is the second leading cause of blindness worldwide. Elevated intraocular pressure (IOP) is a primary risk factor associated with POAG. Increased aqueous humor (AH) outflow resistance through the trabecular meshwork (TM) results in elevated IOP in POAG patients. Resistance to AH outflow is associated with increased accumulation of extracellular matrix (ECM) proteins in the TM. In addition, levels of transforming growth factor-beta2 (TGF-β2) are elevated in the AH and TM tissue of POAG patients. Elevated levels of TGF-β2 in other tissues have been associated with fibrosis and increased tissue stiffness. However, locally produced effectors that maintain homeostatic relationships must also be present. Bone morphogenetic proteins (BMPs) serve this purpose in the TM as they inhibit TGF-β2-induced ECM changes in TM cells. This review article first describes the TGF-β superfamily of growth factors including BMPs and their canonical and noncanonical signaling pathways. The article then addresses the role of TGF-β2 in the pathophysiology of POAG as related to the ECM and ECM crosslinking enzymes. This is followed by a discussion of potential homeostatic control mechanisms of TGF-β2 signaling in the TM including the inhibitory role of BMP-4 and BMP-7. We then describe the relationship of TGF-β2 and BMPs in TM fibrosis including the role of antagonists. Lastly, in future directions, we identify potential future studies that explore new and unique cellular interactions within the TM for potential therapeutic interventions. |
| Databáze: | OpenAIRE |
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