CORNEAL ENDOTHELIAL REPAIR--ROLE OF LIPID MEDIATORS

角膜内皮修复——脂质介质的作用

• 批准号: 2471205
• 负责人: MARCIA M JUMBLATT
• 金额: $ 16.21万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/2471205
• 关键词: age difference; arachidonate; biological signal transduction; cell communication molecule; cell cycle; cell differentiation; cell growth regulation; cell proliferation; ceramides; corneal endothelium; eicosanoids; enzyme mechanism; gene expression; histochemistry /cytochemistry; human tissue; laboratory rabbit; leukotrienes; lipid biosynthesis; lipid metabolism; membrane lipids; organ culture; phospholipids; second messengers; wound healing

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：角膜内皮以规则的单层形式存在。 排列在角膜后方的细胞，并保持 通过从亲水性基质中去除液体来提高角膜透明度，以及 这种组织自我修复的能力随着年龄的增长而减弱。PI的目标是 为了确定衰老如何影响内源性合成的脂质介质 血管内皮细胞功能恢复中的关键作用 受伤。角膜内皮对生物活性脂类的反应和活性 调节它们的内源合成和反应通路 有丝分裂、成熟和死亡的过程。她建议：1)LPA 增加角膜内皮细胞有限的有丝分裂能力，而 2)前列腺素E_2促进屏障功能的发展；3)神经酰胺 调节静止和细胞凋亡的获得。 为了检验这些假设，PI提出了以下几组研究： 1)确定脂质介体对增殖关键步骤的影响； 分化和成熟；2)定义表达和成熟的变化 PGE_2、LPA和PGE_2合成相关酶的分布 成熟时产生的神经酰胺；3)确定是否 膜磷脂的组成随年龄的变化而变化， 增殖状态或损伤；以及4)验证我们的预测，成年人类 角膜内皮细胞表现出相同的LPA、PGE2和 神经酰胺做为兔角膜内皮细胞的成熟培养。这个 这些研究的结果将建议新的补充剂(脂类， 磷脂、脂肪酶)到角膜存储介质和眼内冲洗 将促进创伤和/或老年人功能恢复的解决方案 角膜内皮。