HUMAN CORNEAL ENDOTHELIAL TRANSPLANTATION - A PILOT STUD

人角膜内皮移植——试点项目

• 批准号: 3426280
• 负责人: MICHAEL S INSLER
• 金额: $ 2.1万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1986-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3426280
• 关键词: corneal endothelium; corneal epithelium; human tissue; keratoplasty; newborn human (0-6 weeks); scanning electron microscopy; xenotransplantation

The corneal endothelium of the adult human possesses essentially no regenerative capability; typically, in vivo cell loss is followed by compensatory hypertrophy of the remaining endothelium. This lack of regenerative capacity poses a significant clinical problem, as many corneal diseases are accompanined by endothelial cell loss, resulting in corneal edema. Additionally, certain ophthalmic surgical procedures are associated with significant losses of endothelial cells: penetrating keratoplasty, cataract extraction, and intraocular lens implantation. In most instances, patients with significant corneal edema, secondary to low endothelial cell densities (or endothelial dysfunction) need only have the endothelium replaced to restore corneal clarity. Currently, medical management of endothelial cell loss is limited to penetrating keratoplasty. The establishment of human corneal endothelium in tissue culture and subsequent transplantation to denuded Descemet's membrane, yielding a monolayer of functionally intact cells, would be a breakthrough of major importance. Prolonged cultures of human neonatal corneal endothelium with demonstrated adherence to human corneal buttons denuded of their native endothelium is currently being achieved. So as to evaluate the long term viability and functional integrity of cultured human corneal endothelium in vivo, and provide preliminary data to assess the effectiveness and reproducibility of this approach, a series of experiments have been designed involving transplantation of cultured corneal endothelium into rhesus. Group I will consist of xenografts (human buttons into rhesus) and serve as control for surgical technique. Group II will consist of xenografts lacking endothelium and will serve to confirm the extent of recepient endothelial growth and migration. Group III will consist of xenografts with transplanted corneal endothelium. Clinical evaluation (biomicroscopy, wide-field specular microscopy, tonometry, and pachymetry) will assess the functional integrity of the transplanted endothelium; cell morphology will also be evaluated, as determined by scanning electron microscopy. It is anticipated that the results of these experiments will illuminate the functional status of transplanted endothelial cells, in vivo, and provide pilot data indicating the feasibility of this project on a larger scale.

成年人的角膜内皮基本上没有 再生能力;通常，体内细胞损失之后是 剩余内皮的代偿性肥大。 这种缺乏 再生能力提出了一个重大的临床问题，因为许多角膜 疾病是由内皮细胞损失，导致角膜 水肿 此外，某些眼科手术程序与 内皮细胞的显著损失：穿透性角膜移植术， 白内障摘除和眼内透镜植入。 在大多数情况下， 继发于低内皮细胞的显著角膜水肿患者 密度（或内皮功能障碍）只需要具有内皮 更换以恢复角膜清晰度。 目前，医疗管理 内皮细胞损失限于穿透性角膜移植术。 的 人角膜内皮细胞在组织培养中建立及后续的研究 移植到裸露的后弹力膜上，产生单层的 功能完整的细胞，将是一个重大的突破。 人新生儿角膜内皮细胞的长期培养 粘附于剥除其天然内皮的人角膜扣， 目前正在实现。 以评估长期可行性， 体内培养的人角膜内皮的功能完整性，和 提供初步数据，以评估 这种方法，一系列的实验已经设计，涉及 将培养的角膜内皮细胞移植到恒河猴体内。 第一组将 由异种移植物（人纽扣植入恒河猴）组成，并作为对照， 手术技术。 第二组将包括缺乏 内皮细胞，并将用于确认受体内皮细胞的程度， 增长和迁移。 第III组将由异种移植物组成， 移植的角膜内皮 临床评价（生物显微镜检查， 宽视野镜面反射显微镜检查、眼压测量和角膜厚度测量）将评估 移植内皮的功能完整性;细胞形态将 也可以通过扫描电子显微镜进行评价。 预计这些实验的结果将阐明 移植内皮细胞的功能状态，在体内，并提供 试验数据表明该项目在更大规模上的可行性。