Localization of myocilin/trabecular meshwork-inducible glucocorticoid response protein in the human eye

PURPOSE. To study distribution and cellular localization of myocilin/trabec ular meshwork-inducible glucocorticoid response protein (TIGR) in the human eye. METHODS. A peptide antibody against a portion of the myosin-like domain of myocilin/TIGR was developed. Different ocular tissues from three human dono rs were investigated by one- and two-dimensional gel electrophoresis and We stern blot analysis. Immunohistochemistry was performed on 25 human eyes en ucleated because of posterior choroidal melanoma and on 7 normal human dono r eyes. RESULTS. By Western blot analysis, a band at approximately 57 kDa was visua lized in cornea, trabecular meshwork, lamina cribrosa, optic nerve, retina, iris, ciliary body, and vitreous humor. By immunohistochemistry, immunorea ctivity for myocilin/TIGR was observed in cells of the corneal epi- and end othelium and extracellularly in the corneal stroma and sclera. In the trabe cular meshwork, cells of the uveal and corneoscleral meshwork were stained, as was the cribriform area directly adjacent to Schlemm's canal. Positive staining was seen in cells of the ciliary epithelium, ciliary muscle, lens epithelium, and in stromal and smooth muscle cells of the iris. Throughout the entire vitreous body, fine filamentous material was positively labeled. In the retina, staining was seen along the outer surface of rods and cones , in neurons of the inner and outer nuclear layer, and in the axons of opti c nerve ganglion cells. Optic nerve axons were stained in the prelaminar, l aminar, and postlaminar parts of the nerve. In the region of the lamina cri brosa, astrocytes in the glial columns and cribriform plates were positivel y labeled. CONCLUSIONS. Myocilin/TIGR is expressed in almost every ocular tissue. Depe nding on die respective tissue, it is observed extra- or intracellularly. T he presence of myocilin/TIGR in optic nerve axons and lamina cribrosa astro cytes indicates that the trabecular meshwork might not be the only target o f abnormal myocilin/TIGR in GLC1A-linked open-angle glaucoma.