Glycosaminoglycans Influence Extracellular Matrix of Human Trabecular Meshwork Cells Cultured on 3D Scaffolds.
ACS Biomater Sci Eng
; 8(12): 5221-5232, 2022 Dec 12.
Article
em En
| MEDLINE
| ID: mdl-36384278
ABSTRACT
Glaucoma is a multifactorial progressive optic neuropathy characterized by the loss of retinal ganglion cells leading to irreversible blindness. It is the leading cause of global irreversible blindness and is currently affecting over 70 million people. Elevated intraocular pressure (IOP) is considered the only modifiable risk factor and is a target of numerous treatment modalities. Researchers have assigned this elevation of IOP to accumulation of extracellular matrix (ECM) components in the aqueous humor (AH) outflow pathway. The major drainage structure for AH outflow is the trabecular meshwork (TM). The ECM of the TM is important in regulating IOP in both normal and glaucomatous eyes. In this work, we have studied the role of exogeneous glycosaminoglycans (GAGs), glucocorticoids, and culture conditions on the expression of the ECM gene and proteins by human TM (hTM) cells cultured on biomaterial scaffolds. Gene and protein expression levels of elastin, laminin, and matrix metalloproteinase-2 (MMP-2) were evaluated using quantitative PCR and immunohistochemistry. Pressure gradient changes in cell-laden scaffolds in perfusion cultures were also monitored. Our findings show that GAGs and dexamethasone play an influencing role in hTM ECM turnover at both transcriptional and translational levels by altering expression levels of elastin, laminin, and MMP-2. Understanding the role of exogeneous factors on hTM cell behavior is helpful in gaining insights on glaucoma pathogenesis and ultimately pivotal in development of novel therapeutics against the disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glaucoma
/
Metaloproteinase 2 da Matriz
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article