Expression of the glaucoma gene myocilin ( <i>MYOC</i> ) in the human optic nerve head

Abstract

ABSTRACT Glaucoma is a leading cause of blindness in the world, and several glaucoma genes have been recently identified. The glaucoma gene myocilin ( MYOC ) (also known as GLC1A and TIGR) is responsible for juvenile open‐angle glaucoma and a subset of adult‐onset primary open‐angle glaucoma. Previous studies have shown that MYOC is expressed in the trabecular meshwork, an ocular tissue involved in the development of ocular hypertension, which is often associated with the development of glaucoma. Because all forms of glaucoma involve pathogenic changes to the optic nerve head (ONH), including cupping, excavation, and collapse of the connective support tissue, we sought to determine whether MYOC mRNA and protein are expressed in cells of the human ONH. Reverse transcriptase PCR, in situ hybridization, immunofluorescent microscopy, and immunoblotting of polyacrylamide gels were used to demonstrate that myocilin is expressed in ONH tissue and cultured ONH cells. A secondary purpose was to determine whether MYOC sequence variations are associated with a clinically significant fraction of normal tension glaucoma (NTG), a form of glaucoma in which intraocular pressure is not appreciably elevated. Nonconservative MYOC sequence variations were observed in only 6 of 307 patients with NTG and 4 of 193 control individuals ( P =1.0, Fisher's exact test). Thus, although MYOC is expressed in a pattern that is consistent with its involvement in NTG, variations in the MYOC coding sequence are not commonly or significantly associated with this disease.