title: Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure.
abstract: Optineurin (optic neuropathy inducing protein; OPTN) was recently linked to 16.7% of families with primary open-angle glaucoma. The function of OPTN in the eye is not known, but is present in the trabecular meshwork, which is responsible for maintenance of intraocular pressure (IOP). To gain insight into the role of OPTN in the development of glaucoma we studied its expression in response to factors known to be associated with the disease: elevated IOP, tumor necrosis factor-alpha (TNFalpha), and dexamethasone (DEX). We performed the treatments in human organ cultures under conditions mimicking physiological pressure. We find OPTN significantly upregulated after 2, 4, and 7 days of sustained elevated IOP. OPTN expression is also induced 2.3-fold by TNFalpha and 2.6-fold by prolonged DEX treatment. These results demonstrate that OPTN is part of the transcriptome responding to glaucomatous insults and support the protective role of this protein in the trabecular meshwork.
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Wadsworth Building, Erwin Road, Box 3802, Durham, NC 27710, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Vittitow
authors.forename: Teresa
authors.initials: T
authors.lastname: Borrás
mesh_terms: D000368:Aged; D000869:Anterior Eye Segment / Q000033:anatomy & histology; D018797:Cell Cycle Proteins; D003907:Dexamethasone / Q000494:pharmacology; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005901:Glaucoma / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure; D007700:Kinetics; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism*; D035582:Transcription Factor TFIIIA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C409460:OPTN protein, human; D012333:RNA, Messenger; D035582:Transcription Factor TFIIIA; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone