Cell Biotechnology and Molecular Biology of Presbyacusis-related Gene and Its Clinical Application

由有丝分裂后稳定组织组成的内耳是线粒体DNA （mtDNA）突变的靶器官。为了确定mtDNA突变是否是感音神经性听力损失（SNHL）患者的易感因素，我们评估了60名感音神经性听力损失（SNHL）患者和47名正常对照者的mtDNA^<4977>缺失。所有病例均无耳毒性或噪声暴露史、中耳疾病或其他已知SNHL病因。提取外周血白细胞DNA标本，采用聚合酶链反应检测mtDNA^<4977>缺失。SNHL患者mtDNA^<4977>缺失率显著高于对照组（75% vs 30%, p<0.0001）。mtDNA^<4977>缺失检出率随听力阈值的降低而显著增高。衰老对对照组和SNHL组mtDNA^<4977>缺失的检出率均无影响。我们描述了特发性双侧SNHL患者mtDNA^<4977>缺失的高检出率，并提出（至少）一些晚期SNHL病例应归类为线粒体氧化磷酸化疾病。目前的推断将为治疗和预防SNHL包括老年性痴呆提供新的可能性。研究了老年性耳聋动物模型中老年耳蜗线粒体DNA （mtDNA）的突变。与年轻小鼠相比，老年小鼠的听力明显下降。在老年小鼠耳蜗中检测到高度缺失4802 bp的mtDNA(80%)，而在年轻小鼠耳蜗中未发现mtDNA缺失。这些结果表明，mtDNA缺失有助于老年性痴呆的病理生理过程。

The inner ear composed of a post-mitotic stable tissue is a target organ for mitochondrial DNA (mtDNA) mutation. To determine whether mtDNA mutation is a predisposing factor in patients with sensorineural hearing loss (SNHL), we assessed the mtDNA^<4977> deletion from 60 patients with sensorineural hearing loss (SNHL) and 47 normal controls. All cases had no past history of ototoxic or noise exposure, middle ear disease, or other known etiological factors for SNHL.DNA specmiens extracted from peripheral blood leukocytes were used for detection of mtDNA^<4977> deletion by polymerase chain reaction. Patients with SNHL had a significantly high rate of the mtDNA^<4977> deletion than those of controls (75% vs 30%, p<0.0001). The detection rate of mtDNA^<4977> delection was significantly increased with the deterioration of the hearing threshold. Aging did not influence the detection rate of mtDNA^<4977> deletion in either the control or SNHL group. We have described high detection rates of the mtDNA^<4977> deletion in patients with idiopathic bilateral SNHL and propose that (at least) some of the advanced SNHL cases should be categorized as mitochondrial oxidative phosphorylation diseases. The present inference would offer novel possibilities for treatment and prevention of SNHL including presbycusis.A mutant mitochondrial DNA (mtDNA) was investigated in the aged cochlea of the animal model of presbycusis. The aged mice showed a significant deterioration of hearing compared with the young mice. The mtDNA with a 4802 bp deletion was highly detected in the aged cochlea (80%) whereas no mtDNA deletion was recognized in the young mice. These results indicates that the mtDNA deletion contributes to pathophysiological processes underlying presbycusis.