MOLECULAR BIOLOGY OF DIABETIC CATARACT FORMATION
MOLECULAR BIOLOGY OF DIABETIC CATARACT FORMATION
批准号:
6384483
负责人:
Patrick Ross Cammarata
金额:
$27.76万
依托单位国家:
美国
项目类别:
财政年份:
1990
资助国家:
美国
项目状态:
已结题
起止时间:
1990-07-01 至 2005-05-31
关键词:
aldehyde reductase chloride channels diabetic cataract diacylglycerols disease /disorder model gene expression genetically modified animals immunoelectron microscopy laboratory mouse lens membrane transport proteins model design /development northern blottings osmotic pressure pathologic process polymerase chain reaction sodium taurine tissue /cell culture
中文摘要
描述(改编自申请人摘要):糖尿病性白内障是一种
严重和代价高昂的全球性健康问题。细胞内渗透胁迫
与糖尿病性白内障的病因有关。的定义
导致并发症的基本分子和细胞过程的顺序
糖尿病性白内障的发病率尚未确定。有机物的积累
渗透剂(山梨糖醇、肌醇、牛磺酸)通常保护透镜免受
通过维持细胞内渗透压稳态来调节渗透压失衡。在
在维持透镜内环境稳定的过程中,透镜上皮层保存
本身通过利用几种渗透补偿机制,而
皮下纤维细胞,可能是因为神经调节能力减弱,
肿胀和水泡。为了获得一个现实的观点的病理生理影响,
一种新的糖尿病性白内障转基因动物模型
对探讨渗透压增高的发病机制和治疗有重要意义
白内障形成我们成功地将牛
钠/肌醇协同转运蛋白基因(bSMIT),
显示转基因在发育中的透镜纤维中功能性表达。Lens
纤维肿胀和随后的白内障形成提供了一种生理学上的
模拟人类糖尿病性白内障进展的替代物。小心
对小鼠透镜区域发育和早发性肿胀的仔细检查允许
验证透镜纤维不能
监管机构。转基因植物的分子生物学和病理生理学
显示糖尿病性白内障的小鼠模型将通过关联
通过原位杂交和偶联反向杂交测定bSMIT基因表达水平
转录/聚合酶链反应与晶状体内的内容,
游离肌醇。透镜形态学之后将是光和电子
使用显微镜评价转基因和非转基因同窝仔
胚胎晶状体通过六个月大的老鼠的晶状体。低
转基因表达小鼠,正常饲养时不形成透镜混浊
和饮食,将通过补充肌醇的饮食来这样做。的
确定糖尿病患者病理生理学中的事件顺序
白内障形成将确定干预部位,
开发创新的药物制剂,以预防或阻止
糖尿病性白内障的进展。其中一种干预措施是激活氯化物
通道,其增强氯化物排出和肌醇流出。本研究
建议测试增强肌醇流出的潜在有用性
通过氯离子通道作为药物治疗的手段,
渗透胁迫
英文摘要
DESCRIPTION (Adapted from applicant's abstract): Diabetic cataract is a
significant and costly worldwide health problem. Intracellular osmotic stress
has been implicated in the etiology of diabetic cataract. The definition of the
sequence of basic molecular and cellular processes leading to the complications
of diabetic cataract have yet to be established. The accumulation of organic
osmolytes (sorbitol, myo-inositol, taurine) normally protects the lens against
osmotic imbalance by maintaining intracellular osmotic homoeostasis. In the
course of maintaining lens homeostasis, the lens epithelial layer preserves
itself by utilizing several osmotic compensatory mechanisms, whereas the
subjacent fiber cells, likely because of a diminished capacity to osmoregulate,
swell and bleb. To obtain a realistic view of the pathophysiological impact of
osmotic stress on diabetic cataract formation, a novel transgenic animal model
has been developed useful to exploring the pathogenesis and therapy of osmotic
cataractogenesis. We have successfully introduced the bovine
sodium/myo-inositol cotransporter gene (bSMIT) in several mouse lines and have
shown the transgene is functionally expressed in developing lens fibers. Lens
fiber swelling and consequent cataractous formation provide a physiological
surrogate that simulates the progression of human diabetic cataract. Careful
scrutiny of mouse lens regional development and early-onset swelling allows for
verification of the hypothesis that the lens fibers are incapable of
osmoregulation. The molecular biology and the pathophysiology of the transgenic
mouse model exhibiting diabetic cataract will be linked by correlating the
level of bSMIT gene expression via in situ hybridization and coupled reverse
transcription/polymerase chain reaction with the intralenticular content of
free myo-inositol. Lens morphology will be followed by light and electron
microscopic evaluation of transgenic and nontransgenic littermates using
embryonic lenses up through lenses from six month-old mice. Low
transgene-expressing mice, which do not form lens opacities with normal rearing
and diet, will be made to do so with a myo-inositol supplemented diet. The
determination of the sequence of events in the pathophysiology of diabetic
cataract formation will identify sites of intervention and allow for the
development of innovative pharmacological agents to prevent or halt the
progression of diabetic cataract. One such intervention is to activate chloride
channels, which enhances both chloride exit and myo-inositol efflux. This study
proposes to test the potential usefulness of enhancing myo-inositol efflux
through chloride channels as a means for drug therapy to relieve intrafiber
osmotic stress.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
MOLECULAR BIOLOGY OF SUGAR CATARACT IN LENS CELLS
-
批准号:2654643
-
项目类别:
-
资助金额:$30.61万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MECHANISM OF SUGAR CATARACT FORMATION IN LENS CELLS
-
批准号:3260722
-
项目类别:
-
资助金额:$14.29万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MOLECULAR BIOLOGY OF DIABETIC CATARACT FORMATION
-
批准号:6786771
-
项目类别:
-
资助金额:$25.74万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MECHANISM OF SUGAR CATARACT FORMATION IN LENS CELLS
-
批准号:3260720
-
项目类别:
-
资助金额:$16.79万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MECHANISM OF SUGAR CATARACT FORMATION IN LENS CELLS
-
批准号:2159464
-
项目类别:
-
资助金额:$14.54万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MOLECULAR BIOLOGY OF SUGAR CATARACT IN LENS CELLS
-
批准号:2911286
-
项目类别:
-
资助金额:$1.12万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MECHANISM OF SUGAR CATARACT FORMATION IN LENS CELLS
-
批准号:3260721
-
项目类别:
-
资助金额:$13.86万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MOLECULAR BIOLOGY OF DIABETIC CATARACT FORMATION
-
批准号:6096981
-
项目类别:
-
资助金额:$25.1万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MOLECULAR BIOLOGY OF DIABETIC CATARACT FORMATION
-
批准号:6518340
-
项目类别:
-
资助金额:$25.41万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MOLECULAR BIOLOGY OF SUGAR CATARACT IN LENS CELLS
-
批准号:2159467
-
项目类别:
-
资助金额:$27.81万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MECHANISM OF SUGAR CATARACT FORMATION IN LENS CELLS
-
批准号:3260723
-
项目类别:
-
资助金额:$15.2万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MOLECULAR BIOLOGY OF SUGAR CATARACT IN LENS CELLS
-
批准号:2331623
-
项目类别:
-
资助金额:$27.82万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MOLECULAR BIOLOGY OF DIABETIC CATARACT FORMATION
-
批准号:6635574
-
项目类别:
-
资助金额:$25.58万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
MECHANISM OF SUGAR CATARACT FORMATION IN LENS CELLS
-
批准号:2159465
-
项目类别:
-
资助金额:$2.01万
-
财政年份:1990
-
负责人:Patrick Ross Cammarata
-
依托单位:
STRUCTURAL MOLECULE INTERACTION OF LENS CELL-LENS CAPSUL
-
批准号:3447765
-
项目类别:
-
资助金额:$4.45万
-
财政年份:1984
-
负责人:Patrick Ross Cammarata
-
依托单位:
STRUCTURAL MOLECULE INTERACTION OF LENS CELL-LENS CAPSUL
-
批准号:3447764
-
项目类别:
-
资助金额:$4.27万
-
财政年份:1984
-
负责人:Patrick Ross Cammarata
-
依托单位:
STRUCTURAL MOLECULE INTERACTION OF LENS CELL-LENS CAPSUL
-
批准号:3447766
-
项目类别:
-
资助金额:$3.43万
-
财政年份:1984
-
负责人:Patrick Ross Cammarata
-
依托单位:
海外基金