PATHOGENESIS OF CORNEAL EDEMA AFTER INTRAOCULAR SURGERY

眼内手术后角膜水肿的发病机制

• 批准号: 3255614
• 负责人: HENRY Francis EDELHAUSER
• 金额: $ 25.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3255614
• 关键词: actins; adenosinetriphosphatase; aging; aldehyde reductase; cats; cell morphology; contact lens; cornea edema; corneal endothelium; cytoskeleton; diabetic ophthalmopathy; drug metabolism; eicosanoid metabolism; eicosanoids; electron microscopy; endotoxins; eye surgery; human tissue; laboratory rabbit; laboratory rat; membrane transport proteins; oxidoreductase inhibitor; pathologic process; perfusion; postoperative complications; stainings; wound healing

DESCRIPTION (Investigator's Abstract): The objective is to study the pathogenesis of corneal edema which can occur from disease (i.e., endothelial dystrophies, contact lens wear, diabetes, inflammation) and which occurs following intraocular surgery. Clinically following cataract, vitrectomy and anterior segment surgery, an increase in corneal thickness and loss of endothelial cells occurs, which reflects both a compromised barrier and pump function. A cornea that has presurgical polymegathism appears to also have a greater predisposition toward corneal edema following intraocular surgery, and this is especially true for the diabetic patient, a patient with guttate and may be the case for long term contact lens wearers, all of whom have severe endothelial polymegathism, and are at the age for cataract surgery. The proposed studies should further our understanding of the pathogenesis of corneal edema and the prevention of post-surgical corneal edema. Answers will be sought to the following specific aims: (1) Is polymegathism related to corneal endothelial cytoskeleton change? The corneal endothelium of contact lens wearers, diabetic, age related polymegathism and following wound healing will be studied. Comparison of endothelial volume regulation changes (hrs) will be compared to endothelial cells changes that occur over months and years. The cytoskeleton changes will be measured by NBD-phalloidin staining of the F-actin and quantified by measuring the total F-actin by a DNase I and phalloidin binding assay. (2) The effect of 12(R)HETE which is formed by the corneal epithelium via P450 metabolism of arachidonic acid will be evaluated for its role in altering the endothelial cytoskeleton, pump and barrier function. The diffusion of 12(R)HETE across the cornea, its metabolism and breakdown products will be determined for their role in changing the endothelial metabolic pump function. (3) Is polymegathism associated with alterations in corneal endothelial metabolism as measured by QO2, glucose metabolism, ATPase activity, cAMP/cGMP, protein kinase "C", cytochrome oxidase and mitochondrial NADPH. And (4) what is the effect of endotoxin on the corneal endothelial barrier and pump function? These studies will be performed on in vitro perfused human (obtained from GA Eye Bank) cat (with low cell number), rabbit and rat (normal and diabetic) corneas. The results of these studies should provide a better understanding of the corneal endothelium in post-operative corneal edema and will answer the question if contact lens induced polymegathism will predispose a cornea toward post-operative edema.

描述（研究者摘要）：目的是研究 角膜水肿的发病机理可能由疾病（即， 内皮营养不良、接触透镜配戴、糖尿病、炎症）和 这发生在眼内手术之后。 在临床上， 玻璃体切除术和眼前节手术，角膜厚度增加 和内皮细胞的损失发生，这反映了一个妥协， 屏障和泵功能。 一个角膜，有手术前多巨 似乎也有更大的倾向于角膜水肿 在眼内手术后，这对于糖尿病患者尤其如此。 患者，有点滴的患者，可能是长期接触的情况 透镜配戴者，他们都有严重的内皮细胞多巨症， 白内障手术的年龄。 建议的研究应可进一步促进我们的 了解角膜水肿的发病机制和预防 术后角膜水肿 将寻求以下问题的答案 具体目的：（1）多巨体症是否与角膜内皮细胞 细胞骨架改变？ 接触透镜佩戴者的角膜内皮， 糖尿病、年龄相关性多巨畸形和伤口愈合后， 研究了 将比较内皮容量调节变化（hr） 相比之下，内皮细胞的变化会持续数月甚至数年。 细胞骨架的变化将通过NBD-鬼笔环肽染色来测量。 通过DNA酶I测量总F-肌动蛋白进行定量， 鬼笔环肽结合测定。(2)12（R）HETE的作用是由以下物质形成的： 角膜上皮通过P450代谢花生四烯酸， 评估其在改变内皮细胞骨架、泵和 屏障功能 12（R）HETE穿过角膜的扩散， 代谢和分解产物将被确定其作用， 改变内皮代谢泵功能。 (3)是多巨体症 与角膜内皮代谢的改变相关， 通过QO 2、葡萄糖代谢、ATP酶活性、cAMP/cGMP、蛋白激酶“C”， 细胞色素氧化酶和线粒体NADPH。 （4）什么是影响 内毒素对角膜内皮屏障和泵功能的影响 这些 研究将在体外灌注的人（从GA Eye获得）上进行 Bank）猫（细胞数低）、兔和大鼠（正常和糖尿病） 角膜 这些研究的结果应该提供更好的 对角膜内皮细胞在术后角膜水肿中的认识 并将回答接触透镜引起的多巨畸形是否会 使角膜易于术后水肿。