Application of Two Animal Models in Pursuit of Myopia Control

两种动物模型在近视控制中的应用

• 批准号: 9109113
• 负责人: CHRISTINE FRANCES WILDSOET
• 金额: $ 8.66万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9109113
• 关键词: Address; Adverse effects; Amacrine Cells; Animal Model; Atropine; Categories; Cavia; Cells; Childhood; Clinical; Clinical Trials; Cone; Contact Lenses; Country; Data; Devices; Dose; Epidemic; Exposure to; Eye; Eyedrops; Eyeglasses; Failure; Family; Far East; Frequencies; Gene Expression Profile; Genes; Genetic; Goals; Grant; Growth; Human; Imaging Techniques; Individual; Koreans; Label; Length; Lesion; Light; Lighting; Mediating; Modeling; Molecular Biology; Molecular Biology Techniques; Molecular Profiling; Muscarinic Acetylcholine Receptor; Myopia; Nature; Neurotoxins; Optics; Outcome; Pathway interactions; Peripheral; Pharmaceutical Preparations; Pharmacological Treatment; Phototherapy; Population; Prevalence; Primates; Publishing; Reaction Time; Regimen; Regulatory Pathway; Reporting; Retinal; Role; Sclera; Signal Pathway; Signal Transduction; Site; Structure of retinal pigment epithelium; Technology; Testing; Translating; Treatment Efficacy; Vision; Visual; Work; base; cholinergic; clinically relevant; design; effective therapy; emmetropization; falls; improved; in vivo; insight; lens; male; novel; optical imaging; prevent; public health relevance; research study; response; statistics; tool; treatment effect; young adult

DESCRIPTION (provided by applicant): Myopia (short-sightedness) results from a failure of emmetropization in which eyes grow too long for their optical power. Myopia's association with sight-threatening complications and near-epidemic prevalence in several populations make it critical that effective treatments for slowing myopia progression be developed. The chick eye has provided a very fruitful model, yielding evidence for local retinal control of eye growth, identifying multifocal (MF) optical manipulations that inhibit ocular elongation as potential myopia treatments, and providing initial insights into the mechanism underlying atropine's anti-myopia action. The guinea pig, a mammalian model with a fibrous sclera more like human sclera, has yielded valuable translational data. Our proposal relied on recent findings from many labs, including our own, to develop a multi-pronged approach to myopia control. It exploits novel tools and advanced technologies to pursue 4 aims: (1) We will use our novel optical imaging (cone) devices and MF spectacle lenses combined with neurotoxins to further investigate the mechanisms underlying MF lens effects on eye growth, and the variables influencing treatment efficacy. (2) We will investigate the anti-myopia actions of atropine, to better understand the roles of retinal and nonretinal mechanisms and to determine effective dosing regimens. (3) We will investigate whether treatment efficacy can be improved by combining MF lenses designed to slow myopic growth with either or both atropine and very bright light, which is also known to slow myopia progression. Experiments under Aim 3 will make use of results from earlier experiments (Aims 1 & 2). We will apply molecular biology tools to study retinal/retinal pigment epithelium (RPE) signal pathways. RPE gene expression signatures of myopic and hyperopic growth developed in the last grant period will be exploited to obtain insights into nature of treatment mechanisms and interactions. (4) We will test MF contact lenses in guinea pig to translate our recent related MF spectacle lens studies and look for parallels with chick retinal and RPE molecular signatures that may be applied to understand ocular growth signals.

描述（由申请人提供）：近视（短视野）是由于弹药的失败而导致的，其中眼睛的光功率太长。 在几个人群中，近视与威胁视力并发症的并发症和近流行率的关联使得开发有效的近视发展的有效治疗方法至关重要。 雏鸡的眼睛提供了一个非常富有成果的模型，为局部视网膜对眼睛生长的控制提供了证据，确定了多焦点（MF）光学操纵，可抑制眼部伸长作为潜在的近视治疗，并提供对阿托罗金抗果皮作用的机制的初步见解。 豚鼠是一种具有纤维巩膜的哺乳动物模型，更像人类巩膜，产生了宝贵的翻译数据。 我们的建议依靠许多实验室（包括我们自己的）的最新发现来开发一种多管齐下的近视控制方法。 它利用新颖的工具和先进的技术来追求4个目标：（1）我们将使用新型的光学成像（锥体）设备和MF眼镜镜结合结合神经毒素来进一步研究MF镜头对眼睛生长的影响的机制，以及影响治疗效果的变量。 （2）我们将研究阿托品的抗果皮作用，以更好地了解视网膜和非视网膜机制的作用并确定有效的剂量方案。 （3）我们将通过将旨在减慢近视生长与阿托品和非常明亮的光的MF镜头结合使用，还可以调查是否可以提高治疗疗效，这也已知也会减慢近视的进展。 AIM 3下的实验将利用早期实验的结果（AIMS 1和2）。 我们将应用分子生物学工具来研究视网膜/视网膜色素上皮（RPE）信号途径。 将利用近视和远视增长的RPE基因表达特征，将被利用，以获取对治疗机制和相互作用性质的见解。 （4）我们将测试几内亚猪中的MF隐形眼镜，以翻译我们最近相关的MF眼镜镜头研究，并寻找与鸡视网膜和RPE分子特征的相似之处，这些镜头可以用于了解眼部生长信号。