EXTRACELLULAR MATRIX ABNORMALITIES IN CORNEAL EDEMA

角膜水肿的细胞外基质异常

• 批准号: 2164987
• 负责人: MARIA C KENNEY
• 金额: $ 17.06万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2164987
• 关键词: cell adhesion; cell growth regulation; cell migration; cornea edema; corneal endothelium; corneal epithelium; extracellular matrix proteins; fibrosis; growth factor; human tissue; immunocytochemistry; immunofluorescence technique; in situ hybridization; intraocular aqueous flow; monoclonal antibody; nucleic acid probes; organ culture; pathologic process; protein structure function; tenascin; tissue /cell culture; vision disorders

Pseudophakic and aphakic bullous keratopathy (PBK/ABK) are vision- threatening cornea disorders which are the most common indications for corneal transplantation in the United States. They cause significant visual disabilities that lead to high medical costs for office visits, hospital stays and surgical procedures. Decreased numbers of endothelial cells and/or functional impairment of their fluid pumping ability lead to chronic corneal edema in PBK/ABK corneas. However, our preliminary studies identified major extracellular matrix (ECM) abnormalities in PBK/ABK corneas that cannot be easily explained only by an altered fluid balance. The most striking is the appearance of tenascin, a protein with known antiadhesive properties, which is found in abundance in PBK/ABK corneas but is completely absent from normal corneas. In addition, we found changes of fibronectin, decreased laminin and entactin, and altered collagen phenotype. Take together, these represent a fibrotic process occurring within the PBK/ABK corneas. Our working hypothesis is that tenascin and other abnormal (fibrotic) extracellular matrix found in the pseudophakic/aphakic bullous keratopathy corneas influence adhesives migratory and functional properties of the endothelial cells. In this proposal we will (1) characterize tenascin and ECM components in corneas with early PBK/ABK before transplantation. This will allow us to determine the temporal occurrence of these matrices in relation to the disease progression. We will (2) identify tenascin splice variants since each has unique functional characteristics, and (3) their cellular origin. We will (4) study the influence of tenascin upon the adhesion, migration, growth and fluid pump function of corneal cells. Finally, we will (5) investigate growth factors which are present in the PBK/ABK corneas that may influence tenascin and ECM expression.

假性晶状体眼和无晶状体眼大疱性角膜病 (PBK/ABK) 是视力障碍 威胁性角膜疾病是最常见的适应症 美国角膜移植。它们造成重大 视力障碍导致就诊的高额医疗费用， 住院时间和手术程序。 内皮细胞数量减少和/或功能障碍 它们的液体泵送能力导致 PBK/ABK 的慢性角膜水肿 角膜。然而，我们的初步研究确定了主要的细胞外 PBK/ABK 角膜基质 (ECM) 异常难以轻易解决 只能用液体平衡的改变来解释。最引人注目的是 生腱蛋白（一种具有已知抗粘连特性的蛋白质）的出现， 在 PBK/ABK 角膜中大量存在，但完全不存在 来自正常角膜。此外，我们发现纤连蛋白的变化， 层粘连蛋白和巢蛋白减少，胶原蛋白表型改变。拿 这些共同代表了 PBK/ABK 内发生的纤维化过程 角膜。 我们的工作假设是生腱蛋白和其他异常（纤维化） 人工晶状体/无晶状体大疱中发现细胞外基质 角膜病变角膜影响粘合剂的迁移和功能 内皮细胞的特性。 在本提案中，我们将 (1) 表征生腱蛋白和 ECM 成分 移植前进行早期 PBK/ABK 的角膜。这将使我们能够 确定这些矩阵相对于的时间出现 疾病进展。我们将 (2) 鉴定生腱蛋白剪接变体，因为 每个都有独特的功能特征，以及（3）它们的细胞 起源。我们将（4）研究生腱蛋白对粘附的影响， 角膜细胞的迁移、生长和液体泵功能。最后，我们 (5) 研究 PBK/ABK 中存在的生长因子 可能影响生腱蛋白和 ECM 表达的角膜。