Impact of EOM specific myosin loss on extraocular muscle structure and function

EOM 特异性肌球蛋白损失对眼外肌结构和功能的影响

• 批准号: 8680609
• 负责人: Francisco H Andrade
• 金额: $ 22.39万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680609
• 关键词: 6 year old; ATP phosphohydrolase; Ablation; Address; Adult; Affect; Amblyopia; Appearance; Biochemical; Birth; Characteristics; Child; Data; Defect; Depth Perception; Development; Esotropia; Eye; Eye Movements; Failure; Genes; Goals; Human; Incidence; Intervention; Knockout Mice; Limb structure; Link; Medical; Messenger RNA; Mouse Strains; Mus; Muscle; Muscle Development; Muscle Fibers; Muscle function; Myosin ATPase; Myosin Heavy Chains; Operative Surgical Procedures; Pathway interactions; Patients; Phenotype; Physiological; Positioning Attribute; Property; Protein Isoforms; Proteins; Recovery; Respiratory Muscles; Specimen; Strabismus; Structure; Testing; Therapeutic; Time; Tissues; Vision; Visual; Visual impairment; Work; base; experience; interest; mouse development; muscle form; muscular structure; novel; orbit muscle; postnatal; public health relevance; research study

DESCRIPTION (provided by applicant): Strabismus is a common condition in children that frequently leads to permanent visual impairment. Available treatment options target the extraocular muscles when they are not fully developed. The extraocular muscles are different from other muscles; they even have their own tissue-specific myosin isoform, EOM-specific myosin, which appears soon after birth during a period of postnatal extraocular muscle development linked to visual experience: absence of vision during this time disrupts EOM-specific myosin expression and alters the contractile properties of the extraocular muscles, perhaps permanently. The same changes occur in strabismus patients, and may explain the need for multiple surgeries to restore normal eye position in many of them. This project will answer two questions: to what extent EOM-specific myosin defines normal extraocular muscle function, and how eye muscle function changes when the expression of this tissue-specific myosin is altered. To address these issues, we will ablate or restore the EOM-specific myosin gene to test the relevance of this myosin isoform to extraocular muscle function and integrity. The experimental approach relies on our recently developed mouse strains that permit control of the expression of the EOM-specific myosin gene, and will test the hypothesis that EOM-specific myosin is necessary for normal development of extraocular muscle structure and function, and its appearance after its normal postnatal window does not restore muscle function. Specific Aim 2 will determine the consequences of EOM-specific myosin gene ablation on the postnatal development of mouse extraocular muscle structure and function. Specific Aim 2 will test whether the recovery of EOM-specific myosin expression in the adult mouse restores extraocular muscle function. The answers that will result from the completion of this project will inform the timing of surgical and medical treatment for congenital strabismus.

描述（由申请人提供）：斜视是儿童常见的疾病，经常导致永久性视力障碍。可用的治疗方案针对眼外肌未完全发育时。眼外肌与其他肌肉不同;它们甚至有自己的组织特异性肌球蛋白亚型，即眼外肌特异性肌球蛋白，在出生后不久的一段与视觉经验相关的出生后眼外肌发育期间出现：在此期间缺乏视觉会破坏眼外肌特异性肌球蛋白的表达并改变眼外肌的收缩特性，可能是永久性的。同样的变化也发生在斜视患者身上，这可能解释了为什么他们中的许多人需要多次手术来恢复正常的眼睛位置。这个项目将回答两个问题：在何种程度上眼外肌特异性肌球蛋白定义正常的眼外肌功能，以及当这种组织特异性肌球蛋白的表达改变时，眼肌功能如何变化。为了解决这些问题，我们将切除或恢复眼外肌特异性肌球蛋白基因，以测试这种肌球蛋白亚型与眼外肌功能和完整性的相关性。实验方法依赖于我们最近开发的小鼠品系，允许控制EOM特异性肌球蛋白基因的表达，并将测试假设EOM特异性肌球蛋白是必要的眼外肌结构和功能的正常发育，其外观后，其正常的出生后窗口不恢复肌肉功能。具体目标2将确定眼外肌特异性肌球蛋白基因消融对小鼠眼外肌结构和功能的出生后发育的后果。特定目标2将测试成年小鼠中EOM特异性肌球蛋白表达的恢复是否恢复眼外肌功能。这个项目的完成将为先天性斜视的手术和药物治疗提供信息。