Molecular biology of deafness in the Meniere's Model

描述（由申请人提供）：该项目的目标是更好地了解内耳淋巴水肿引起的分子生物学变化。内淋巴水肿是一种已知的伴随梅尼埃氏病的疾病，这是一种影响数百万美国人的常见疾病。梅尼埃氏病会导致听力丧失和眩晕。虽然眩晕已被证明可以通过许多医疗和手术干预来控制，但听力损失和随后的耳聋尚无已知的治疗方法。这在一定程度上是由于缺乏对梅尼埃氏病相关淋巴内积液听力损失的确切机制的了解。更好地了解与水相关的听力损失的机制将对指导治疗的发展以预防这种听力损失具有重要意义。谷氨酸和其他兴奋性氨基酸（EAA）受体存在于哺乳动物内耳中，被认为在正常听力中起关键作用，但当EAA水平升高时，也与兴奋性毒性损伤有关。在梅尼埃病患者耳蜗和内淋巴积液动物模型中已经有神经元发现，这些发现表明EAA毒性可能在介导相关内耳损伤和随后的听力损失中起重要作用。该项目的具体目标包括研究豚鼠手术诱导的内淋巴积液的著名模型。一旦建立了内淋巴水肿，将收集内耳组织样本并进行分子生物学技术，以确定是否对EAA生理至关重要的基因信使RNA水平。是上调还是下调。这将为更好地理解在这种情况下被激活的确切生化途径提供线索，并可能提供新的治疗策略。预计该项目将在未来获得更大的资助，用于探索和定义与梅尼埃氏相关的内淋巴积液伴随的整个生化变化级联，并可能有朝一日为梅尼埃氏相关听力损失患者提供更好的治疗方案。

DESCRIPTION (provided by applicant): The goal for this project is to better understand the molecular biological changes that occur in the inner ear as a result of endolymphatic hydrops. Endolymphatic hydrops is a condition known to accompany Meniere's disease, a common disorder affecting millions of Americans. Meniere's disease causes both hearing loss and vertigo. Although vertigo has been shown to be controlled via numerous medical and surgical interventions, the hearing loss and subsequent deafness have no known treatment. This is in part due to the lack of knowledge regarding the exact mechanism of hearing loss in Meniere's related endolymphatic hydrops. Better understanding of the mechanisms of hydrops related hearing loss will be important in guiding the development of therapies to prevent such hearing loss. Glutamate and other excitatory amino acid (EAA) receptors are present in the mammalian inner ear and are thought to play a key role in normal hearing but are also implicated in excitotoxic injury when EAA levels are elevated. Neuronal findings have been described in the cochleas of patients with Meniere's disease and animal models of endolymphatic hydrops and these findings suggest that EAA toxicity may be playing an important role in the mediation of associated inner ear injury and subsequent hearing loss. The specific goals of the project include studies of a well-known model of surgically induced endolymphatic hydrops in the guinea pig. Once endolymphatic hydrops has been established, inner ear tissue samples will be collected and subjected to molecular biological techniques that allow for determination of whether messenger RNA levels of genes critical to EAA physiology .are up-regulated or down-regulated. This will provide clues to better understand the exact biochemical pathways that are activated in this condition and possibly provide new treatment strategies to be developed. It is expected that this project will lead to a larger grant in the future that explores and defines the entire cascade of biochemical changes accompanying Meniere's related endolymphatic hydrops and could someday provide better treatment alternatives to patients with Meniere's related hearing loss.