The effects of myocilin expression on functionally relevant trabecular meshwork genes: a mini-review.

Abstract

Myocilin is a secreted glaucoma-associated protein, specifically induced by dexamethasone in human trabecular meshwork cells, where it was discovered. Myocilin is expressed in several tissues of the body, but it causes disease only in the eye. The protein contains two domains: an N-terminal region with significant homologies to nonmuscle myosin, and a C-terminal region, which is similar to the olfactomedin proteins. Forty percent of myocilin undergoes an intracellular endoproteolytic cleavage by calpain II, a calcium-dependent cysteine protease, which releases the 2 domains. The protein is known to interact with intracellular and extracellular matrix proteins, and some is released into the extracellular space associated with exosomes. Myocilin mutations are linked to glaucoma and induce elevated intraocular pressure. Most of the glaucoma-causative mutations map to the olfactomedin domain, which appears to be a critical domain for the function of the protein. Myocilin mutants are misfolded, aggregate in the endoplasmic reticulum, and are not secreted. Overexpression of myocilin and of its mutants in primary human trabecular meshwork cells triggers changes in the expression of numerous genes, many of which have been known to be involved in mechanisms important for the physiology and pathology of the tissue. Here we review recent studies from our laboratory and those of others that deal with trabecular meshwork genes, which are altered by the overexpression of wild-type and glaucoma-causative mutant myocilin genes.

• Authors: Teresa Borrás
• Journal: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (J Ocul Pharmacol Ther) 2014 Mar-Apr Vol. 30 Issue 2-3 Pg. 202-12 ISSN: 1557-7732 [Electronic] United States
• PMID: 24564495 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cytoskeletal Proteins
• Extracellular Matrix Proteins
• Eye Proteins
• Glycoproteins
• olfactomedin
• trabecular meshwork-induced glucocorticoid response protein

Topics

• Animals
• Cytoskeletal Proteins (genetics)
• Extracellular Matrix Proteins (metabolism)
• Eye Proteins (genetics)
• Gene Expression Regulation
• Glaucoma (genetics, pathology)
• Glycoproteins (genetics, metabolism)
• Humans
• Intraocular Pressure (genetics)
• Mutation
• Trabecular Meshwork (metabolism)