Rezaie Tayebeh, Child Anne, Hitchings Roger, Brice Glen, Miller Lauri, Coca-Prados Miguel, Héon Elise, Krupin Theodore, Ritch Robert, Kreutzer Donald, Crick R Pitts, Sarfarazi Mansoor
Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.
Science. 2002 Feb 8;295(5557):1077-9. doi: 10.1126/science.1066901.
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.
原发性开角型青光眼（POAG）在全球影响着3300万人，是导致失明的主要原因。在一项对54个常染色体显性遗传的成人发病型POAG家族的研究中，我们在10号染色体p14上鉴定出致病基因，并将其命名为OPTN（视神经萎缩蛋白）。在16.7%的遗传性POAG家族中发现了OPTN的序列改变，包括眼压正常的个体。OPTN基因编码一种功能未知的保守的66千道尔顿蛋白，该蛋白与肿瘤坏死因子-α信号通路有关，并与多种蛋白质相互作用，包括亨廷顿蛋白、Ras相关蛋白RAB8和转录因子IIIA。视神经萎缩蛋白在小梁网、非色素睫状上皮细胞层、视网膜和大脑中表达，我们推测它发挥着神经保护作用。
