Showing papers by "John H. Fingert published in 2000"

Localization of MYOC transcripts in human eye and optic nerve by in situ hybridization.

Abstract: Purpose To evaluate MYOC (myocilin) gene expression at the RNA level in normal intact human eyes and optic nerve using in situ hybridization. Methods Normal human eyes and optic nerves from donors 62 to 83 years of age with no history of glaucoma were fixed, embedded in paraffin, and sectioned. Sections were hybridized with (35)S-labeled sense and antisense riboprobes derived from a full-length MYOC cDNA. Results High levels of MYOC expression were observed throughout the trabecular meshwork as well as in the most anterior nonfiltering meshwork (Schwalbe's line), in the scleral spur, and in the endothelial lining of Schlemm's canal. MYOC transcripts were also detected in the anterior corneal stroma, in the ciliary muscle, beneath the anterior border of the iris, in the iris stroma, and in the sclera. Expression in the retrolaminar region of the optic nerve was present in the pial septa that divide the nerve fiber bundles, in the perivascular connective tissue surrounding the central retinal vessels, and in the dura mater, arachnoid, and pia mater of the meningeal sheath surrounding the optic nerve. Conclusions MYOC gene expression in the trabecular meshwork, Schlemm's canal, scleral spur, and ciliary muscle indicates a structural or functional role for myocilin in the regulation of aqueous humor outflow that may influence intraocular pressure. MYOC expression in the optic nerve suggests that changes in the structural, metabolic, or neurotropic support of the optic nerve may influence its susceptibility to glaucomatous damage.

The genetic aspects of adult-onset glaucoma: a perspective from the Greater Toronto area.

Abstract: Background: The myocilin gene is the first glaucoma gene to be associated with primary open-angle glaucoma (POAG). The hereditary subset of POAG and the role of the myocilin gene in our population are not clearly defined. Identification of cases of hereditary glaucoma and a better appreciation of the role of the myocilin gene may allow earlier diagnosis of the disease and optimize management of those at risk for glaucoma. Methods: Patients were recruited from university glaucoma practices in the Greater Toronto area from 1996 to 1998. Pedigree analysis and DNA banking were performed for each participant. Mutational analysis of the myocilin gene by means of single-strand conformation polymorphism analysis and direct sequencing was completed for 140 probands with POAG of diverse ethnic background. Results: A total of 103 patients (55.7%) had a family history of glaucoma. Diseasecausing mutations of the myocilin gene were observed in 7 (5.0%) of the 140 probands, which accounted for 6.5% (5/77) of the familial cases. Most mutations were associated with familial disease, which implies a 50% risk of transmission of a high-risk factor for glaucoma. Interpretation: The hereditary subset of POAG is significant, and heritable glaucoma should always be suspected. In spite of the diversity of the ethnic background of our subjects, the observed prevalence of myocilin gene mutations was comparable to that previously reported, and such mutations do not appear to spare any ethnic group.

Characterization of a Large Family with Adult-Onset Primary Open-Angle Glaucoma Caused by a Mutation in the GLC1A Gene

Abstract: In 1997, Stone and colleagues discovered that a gene (GLC1A) on the long arm of chromosome 1 caused a large percentage of autosomal dominant juvenile-onset primary open-angle glaucoma (POAG). GLC1A encodes a 57-kDa protein, known as myocilin, which is expressed in the trabecular meshwork, ciliary body, retina, and 17 of 23 other organs throughout the body (Fingert et al. 1998). In the trabecular meshwork, myocilin production can be induced by corticosteroids, leading some to call it trabecular-meshwork inducible glucocorticoid response (TIGR) protein (Polansky et al. 1997).