title: Optineurin in primary open angle glaucoma.
abstract: The authors' initial estimate indicated that mutations in Optineurin are responsible for a significant proportion of LPG/POAG families. Currently, there are up to 1.2 million persons with LPG and up to 2.47 million persons with POAG in the United States alone. Perhaps twice as many individuals are already affected with this condition without any identifiable clinical signs or symptoms. Investigators are eagerly awaiting confirmation of OPTN mutations in other glaucoma populations. Although additional mutations have already been identified in the sporadic cases of LPG, the significance of this gene in high-pressure POAG requires more intensive investigation. Limited data on partial screening of this gene indicate that OPTN mutations are responsible for a limited number of cases of high-pressure POAG. If the reported mutation rates of OPTN in the LPG group can be confirmed in other LPG or POAG patients, then this gene would be useful in diagnosing presymptomatic persons many decades before they develop this silent and blinding eye condition. Early identification of such at-risk patients would provide an opportunity for immediate targeted medical treatments and specific glaucoma therapy that might significantly delay or completely stop the gradual progression of this condition. Therefore, identification of glaucoma-causing genes such as Myocilin, Optineurin, and others could provide molecular diagnostic tools for this category of optic neuropathy. Although patients with advanced glaucoma will not directly benefit from the use of such molecular diagnostic tools, their immediate family members could certainly benefit from the identification of the cause of the glaucoma decades before the first manifestation of the disease. In summary, a series of mutations in the Optineurin gene have been shown to be the principal cause of adult-onset LPG/POAG phenotype in certain pedigrees. The exact mechanisms through which these mutations lead to the development of glaucoma require additional functional study. The existing evidence suggests that direct interaction of Optineurin with E3-14.7K protein probably utilizes TNF-alpha or Fas-ligand pathways to mediate apoptosis, inflammation, or vasoconstriction. Optineurin also functions through its interactions with other proteins in cellular morphogenesis and membrane trafficking (RAB8), vesicle trafficking (Huntingtin), transcription activation (TFIIIA), and assembly or activity of two unknown kinases. Identification of Optineurin as an adult-onset glaucoma gene and its known interaction with a group of proteins provides the first opportunity to study biochemical pathways that are thought to be involved in causation of this group of eye disorders. Furthermore, identification of this gene as a contributing factor to the development of glaucoma gives a useful tool for screening of this disorder in the elderly population and other high-risk individuals. The exact impact of OPTN in the development of all glaucoma phenotypes requires future study.
authors.affiliation: Molecular Ophthalmic Genetics Laboratory, University of Connecticut Health Center, Farmington, CT 06030, USA. mansoor@neuron.uchc.edu
authors.forename: Mansoor
authors.initials: M
authors.lastname: Sarfarazi
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Rezaie
mesh_terms: D018797:Cell Cycle Proteins; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D035582:Transcription Factor TFIIIA
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D005819:Genetic Markers; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA