Abstract
Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Alternative Splicing
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Amino Acid Sequence
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Brain / metabolism
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Cell Cycle Proteins
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Chromosome Mapping
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Chromosomes, Human, Pair 10 / genetics
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Ciliary Body / metabolism
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Exons
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Eye Proteins / analysis
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Eye Proteins / chemistry
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Eye Proteins / genetics*
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Eye Proteins / physiology
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Female
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Glaucoma, Open-Angle / genetics*
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Golgi Apparatus / chemistry
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Heterozygote
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Humans
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Intraocular Pressure
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Male
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Membrane Transport Proteins
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Middle Aged
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Mutation*
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Mutation, Missense*
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / physiology
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Ocular Hypertension / genetics
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Pedigree
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Polymorphism, Single-Stranded Conformational
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Retina / metabolism
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Trabecular Meshwork / metabolism
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Transcription Factor TFIIIA*
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Zinc Fingers
Substances
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Cell Cycle Proteins
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Eye Proteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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OPTN protein, human
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Transcription Factor TFIIIA