Structural, mechanical, and cell biological properties of the ciliary zonule

睫状小带的结构、机械和细胞生物学特性

基本信息

  • 批准号:
    10587185
  • 负责人:
  • 金额:
    $ 49.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-06-01 至 2028-02-29
  • 项目状态:
    未结题

项目摘要

Project Summary The fibers of the ciliary zonule suspend the lens on the optical axis and transmit the forces that flatten it during disaccommodation. Mutations in genes encoding zonular proteins underlie syndromic and non-syndromic conditions that affect the eye profoundly. Common ocular phenotypes include ectopia lentis (lens dislocation), cataract, axial elongation, myopia, glaucoma, and retinal detachment. The molecular composition of the zonule was recently elucidated, but the mechanism by which mutations in zonular components culminate in structural failure of the fibers is unknown. In Aim 1, therefore, three zonulopathies (Marfan Syndrome, Weill-Marchesani Syndrome, and Isolated Ectopia Lentis) will be modeled in mice. Utilizing recently developed imaging and material testing techniques, we will examine how, in each case, the structure and viscoelastic properties of the mouse zonule are affected by the presence of the mutant protein (or absence of the wild-type protein). We hypothesize that the initial pressurization of the eye is a critical step in zonule development. In Aim 2, this notion will be tested by measuring the rise in intraocular pressure in postnatal mice and determining whether pressurization of the developing eye in vitro causes precocious deployment of zonular fibers. Preliminary studies identified the cross-linking enzyme lysyl oxidase-like-1 (LOXL1) as an abundant component of the zonule proteome. In Aim 3, we propose that LOXL1-derived cross-links have a critical role in strengthening the zonule. We will test that hypothesis in a knockout mouse model. Finally, microspherophakia (i.e., the presence of a smaller and more spherical lens) is observed in Weill-Marchesani patients (who harbor mutations in LTBP2 or FBN1, zonular proteins that contribute to the tensile properties of the fibers). We hypothesize that forces exerted by the zonular fibers on the lens surface influence lens growth. In Aim 4, we will elucidate the three dimensional structure of the human zonule and correlate the distribution of proliferating lens epithelial cells with the strain fields established around zonular attachment points.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Steven Bassnett其他文献

Steven Bassnett的其他文献

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{{ truncateString('Steven Bassnett', 18)}}的其他基金

STRUCTURAL, MECHANICAL, AND CELL BIOLOGICAL PROPERTIES OF THE CILIARY ZONULE
睫状带的结构、机械和细胞生物学特性
  • 批准号:
    10155492
  • 财政年份:
    2018
  • 资助金额:
    $ 49.92万
  • 项目类别:
Role of Microfibrils in the Biology and Pathology of the Eye
微原纤维在眼睛生物学和病理学中的作用
  • 批准号:
    8751961
  • 财政年份:
    2014
  • 资助金额:
    $ 49.92万
  • 项目类别:
Role of Microfibrils in the Biology and Pathology of the Eye
微原纤维在眼睛生物学和病理学中的作用
  • 批准号:
    9127267
  • 财政年份:
    2014
  • 资助金额:
    $ 49.92万
  • 项目类别:
CONFOCAL INTEGRATED INSTRUMENT SYSTEM
共焦集成仪器系统
  • 批准号:
    7793966
  • 财政年份:
    2010
  • 资助金额:
    $ 49.92万
  • 项目类别:
LIM2 AND THE LENS CORE SYNCYTIUM
LIM2 和晶状体核心合胞体
  • 批准号:
    7522631
  • 财政年份:
    2008
  • 资助金额:
    $ 49.92万
  • 项目类别:
LIM2 AND THE LENS CORE SYNCYTIUM
LIM2 和晶状体核心合胞体
  • 批准号:
    7943578
  • 财政年份:
    2008
  • 资助金额:
    $ 49.92万
  • 项目类别:
LIM2 AND THE LENS CORE SYNCYTIUM
LIM2 和晶状体核心合胞体
  • 批准号:
    7661455
  • 财政年份:
    2008
  • 资助金额:
    $ 49.92万
  • 项目类别:
LIM2 AND THE LENS CORE SYNCYTIUM
LIM2 和晶状体核心合胞体
  • 批准号:
    8122176
  • 财政年份:
    2008
  • 资助金额:
    $ 49.92万
  • 项目类别:
LIM2 AND THE LENS CORE SYNCYTIUM
LIM2 和晶状体核心合胞体
  • 批准号:
    7881530
  • 财政年份:
    2008
  • 资助金额:
    $ 49.92万
  • 项目类别:
LIM2 AND THE LENS CORE SYNCYTIUM
LIM2 和晶状体核心合胞体
  • 批准号:
    8323432
  • 财政年份:
    2008
  • 资助金额:
    $ 49.92万
  • 项目类别:

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激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
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