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CORNEAL ENDOTHELIAL REPAIR--ROLE OF LIPID MEDIATORS

角膜内皮修复——脂质介质的作用

基本信息

批准号：
6125085
负责人：
MARCIA M JUMBLATT
金额：
$ 16.36万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-01-01 至 2000-11-30
项目状态：
已结题

项目摘要

DESCRIPTION: The corneal endothelium exists as a monolayer of regularly arranged cells lining the posterior aspect of the cornea and maintains corneal transparency by removing fluid from the hydrophilic stroma, and the ability of this tissue to repair itself decreases with age. The PI goal is to determine how aging affects endogenously synthesized lipid mediators that play a key role in the functional recovery of the endothelium following injury. The corneal endothelium responds to bioactive lipids and actively regulates their endogenous synthesis and response pathways during the processes of mitosis, maturation and death. She proposes: 1)that LPA augments the limited mitotic capacity of the corneal endothelium, while 2)PGE2 promotes the development of the barrier function and 3) ceramide regulates acquisition of quiescence and apoptosis. To test these hypotheses, the PI proposes the following sets of studies: 1)Define the effects of lipid mediators on key steps in proliferation, differentiation and maturation; 2) Define the alterations in expression and distribution of the enzymes involved in the synthesis of PGE2, LPA and ceramide that occur in response to maturation; 3)Determine if the composition of membrane phospholipids changes as a result of age, proliferative status or injury; and 4)Test our prediction that adult human corneal endothelial cells exhibit the same profiles of LPA, PGE2 and ceramide as do mature culture of rabbit corneal endothelial cells. The outcome of these studies will suggest novel supplements (lipids, phospholipids, lipases) to corneal storage media and intraocular irrigation solutions which will promote functional recovery of traumatized and/or aged corneal endothelium.

描述：角膜内皮细胞以规则的单层存在，排列的细胞排列在角膜的后部并维持通过从亲水性基质中去除液体来提高角膜透明度，这种组织的自我修复能力随着年龄的增长而下降。 PI的目标是以确定衰老如何影响内源性合成的脂质介质，在以下内皮功能恢复中起关键作用损伤角膜内皮对生物活性脂质有反应，调节其内源性合成和反应途径，有丝分裂、成熟和死亡的过程。她建议：1）LPA 增强角膜内皮有限的有丝分裂能力， 2）PGE 2促进屏障功能的发展和3）神经酰胺调节静止和凋亡的获得。为了检验这些假设，PI提出了以下几组研究： 1)定义脂质介质对增殖关键步骤的影响，分化和成熟; 2）定义表达的改变，参与PGE 2、LPA和LPA合成的酶的分布神经酰胺发生在成熟的反应; 3）确定是否膜磷脂的组成由于年龄而改变，增殖状态或损伤;和4）测试我们的预测，成年人角膜内皮细胞表现出相同的LPA，PGE 2和神经酰胺和成熟培养的兔角膜内皮细胞一样。的这些研究的结果将提示新的补充剂（脂质，磷脂、脂肪酶）至角膜储存介质和眼内冲洗促进创伤和/或老年人功能恢复的解决方案角膜内皮