Diurnal Rhythms Gene Expression in the Anterior Eye

前眼的昼夜节律基因表达

• 批准号: 7186878
• 负责人: CHARLES J WEITZ
• 金额: $ 25.35万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7186878
• 关键词: Anterior; Anterior eyeball segment structure; Applications Grants; Aqueous Humor; Biological Assay; Blindness; Ciliary epithelium; Circadian Rhythms; Classification; Condition; Daily; Data; Data Set; Databases; Development; Diagnosis; Eye; Gene Expression; Genes; Genome; Glaucoma; Goals; Hour; In Situ Hybridization; Knowledge; Metabolism; Microarray Analysis; Molecular; Mus; Mutant Strains Mice; Neural Retina; Ocular Physiology; Pathway interactions; Periodicity; Physiologic Intraocular Pressure; Physiological; Polymerase Chain Reaction; Process; Production; Publishing; Regulation; Research Personnel; Research Project Grants; Risk Factors; Route; Screening procedure; Site; Structure; System; Therapeutic; Time; Tissues; Transcriptional Regulation; Work; base; circadian pacemaker; expectation; lens; prevent; programs; research study

DESCRIPTION: Elevated intraocular pressure is a major risk factor for glaucoma, and pharmacological reduction of intraocular pressure is the most important therapeutic strategy available for treating glaucoma and preventing progression to blindness. Although there has been recent progress in understanding how tissues of the anterior segment regulate production and outflow of aqueous humor, the processes that determine intraocular pressure, there is at present a poor understanding of these processes at the molecular level. It is likely that detailed knowledge of the molecular mechanisms of aqueous humor regulation in the anterior eye will ultimately offer new and better ways to diagnose and treat glaucoma. Intraocular pressure, like many other important aspects of ocular physiology, is regulated by the circadian system, the hallmark of which is a 24-hour periodicity. This periodicity is generated by an endogenous circadian oscillator, and under conditions of a daily light-dark cycle it is referred to as a "diurnal rhythm." The predominant form of regulation of physiological pathways by the circadian system appears to be at the transcriptional level, with hundreds-to-thousands of genes showing a daily rhythm of expression in various mammalian tissues. It seems likely that the diurnal rhythm of intraocular pressure reflects diurnal transcriptional regulation of genes involved in aqueous humor regulation by tissues of the anterior segment. In this exploratory/developmental research grant application, we propose to identify genes showing a diurnal rhythm of expression in structures of the anterior segment of the mouse eye, particularly those sites relevant to the regulation of intraocular pressure. In previous work, not yet published, we used whole-genome microarray analysis to identify over a thousand genes showing a significant diurnal rhythm of expression in the mouse eye. Using this dataset as a starting point, we propose here to examine a significant subset of the genes for rhythmic expression in the anterior segment, particularly the ciliary epithelium, the site of aqueous humor production. This effort could prove a valuable route to discovering genes and molecular pathways regulating aqueous humor production and intraocular pressure.

产品说明：眼内压升高是青光眼的主要危险因素，药物降低眼内压是治疗青光眼和预防失明进展的最重要治疗策略。虽然最近在了解眼前节组织如何调节房水的产生和流出方面取得了进展，但目前在分子水平上对这些过程的理解还很差。对前眼房水调节的分子机制的详细了解可能最终会为青光眼的诊断和治疗提供新的更好的方法。眼内压，像许多其他重要方面的眼部生理学，是由昼夜节律系统，其标志是一个24小时的周期性。这种周期性是由内源性昼夜节律振荡器产生的，并且在每日光暗循环的条件下，它被称为“昼夜节律”。“昼夜节律系统对生理途径的主要调节形式似乎是在转录水平上，数百至数千个基因在各种哺乳动物组织中显示出每日的表达节奏。眼内压的昼夜节律似乎反映了参与眼前节组织的房水调节的基因的昼夜转录调节。在这个探索性/发展性研究资助申请中，我们建议鉴定在小鼠眼前段结构中表现出昼夜节律表达的基因，特别是与眼内压调节相关的那些位点。在以前的工作中，尚未发表，我们使用全基因组微阵列分析，以确定超过1000个基因表现出显着的昼夜节律的表达在小鼠的眼睛。使用这个数据集作为一个起点，我们建议在这里检查一个显着的子集的基因在前段，特别是睫状体上皮细胞，水状体生产的网站的节奏表达。这一努力可能被证明是发现调节房水产生和眼内压的基因和分子途径的有价值的途径。