Purpose: To elucidate protein expression, genomic structure, and genomic polymorphisms of a novel gene, 'oculomedin', that has been cloned as a mechanical stretch-response gene from human trabecular cells in culture. Methods: Polyclonal antibody was prepared by immunizing rabbits with a chemically synthesized 15-mer peptide of oculomedin. Protein expression was revealed by Western blot analysis after polyacrylamide gel electrophoresis of extracts of mechanically stretched trabecular cells and control trabecular cells in culture as well as retinal tissue. Protein localization was studied immunohistochemically in the human eye section. Genomic structure was determined by searching the GenBank database. Genomic polymorphisms of the coding region in 163 glaucoma patients and 50 normal subjects were detected by PCR amplification and direct sequencing. Results: Western blot analysis showed that oculomedin protein was expressed only in stretched trabecular cells, not in control trabecular cells in culture. Immunohistochemically, oculomedin protein was localized to the trabecular meshwork, Schlemm's canal endothelium, retinal photoreceptor cells, and corneal and conjunctival epithelium. The oculomedin gene (OCLM) consists of two exons which are located inside an intron of a different gene of unknown function (C1orf27) on chromosome 1q25, near and telomeric to myocilin (MYOC). Two types of heterozygous nucleotide substitutions resulting in amino acid changes were found in two of 75 patients with primary open-angle glaucoma, but not at all in patients with other types of glaucoma or in normal subjects. Conclusions: Oculomedin may play a role in the function of the trabecular meshwork and also in the development of primary open-angle glaucoma.