TRANSPLANTATION OF CULTURED CORNEAL ENDOTHELIUM

培养角膜内皮移植

• 批准号: 3264644
• 负责人: MICHAEL S INSLER
• 金额: $ 13.59万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3264644
• 关键词: cell cycle; cornea disorder; corneal endothelium; epidermal growth factor; eye transplantation; fibroblast growth factor; flow cytometry; fluorescence microscopy; growth factor receptors; growth media; homologous transplantation; intercellular connection; keratoplasty; light microscopy; organ culture; receptor expression; scanning electron microscopy; tissue /cell culture; wound healing

The corneal endothelium of man possesses essentially no regenerative capabilities; 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 accompanied by substantial endothelial cell loss, eventually resulting in irreversible corneal edema. Presently, clinical replacement of the corneal endothelium is achieved by homotransplantation of healthy donor corneas. Conventional replacement therapy, however, has placed moderate limitations on the quality and number of donor corneas presently suitable for keratoplasty. With the eventual goal of increasing the potential pool of donor corneas available for transplantation purposes, we propose a set of experiments designed to augment/enhance existing donor corneas. These studies are supplemental to our ongoing studies of endothelial seeding (where there is complete replacement of the donor endothelial monolayer) and are designed to increase the endothelial cell densities of normal (suitable) tissue and low density corneas which otherwise would not be suitable for penetrating keratoplasty. In addition to the potential for increasing the supply of tissue by improving the quality of low density donor corneas, any increase in the cell density of the endothelial monolayer will provide greater endothelial reserve following penetrating keratoplasty. Endothelial cell loss following penetrating keratoplasty shows a significant one year cell loss of 33-45%. This leaves very little endothelial reserve for future demands on the traumatized endothelium following penetrating keratoplasty. Our proposed experiments involving the addition of EGF and/or FGF to cell suspensions, and augmentation of existing monolayers with exogenous cells are all designed to Increase the endothelial cell density of corneas prior to corneal transplantation. The potential human applications of these results have far reaching clinical implications. The replacement of a damaged (diseased) endothelium with a viable cell cultured endothelium (establish human cryopreserved corneal endothelial cell banks) to repopulate aging or diseased corneas prior to, during, or in place of penetrating keratoplasty would dramatically increase the number of corneas suitable for transplantation, provide a means of standardizing the established population of donor preparations and increase the safety and success of future human corneal transplant surgery.

人的角膜内皮基本上不具有再生能力 能力；通常，体内细胞损失之后是补偿性的 剩余内皮细胞肥大。 这种缺乏再生能力 由于许多角膜疾病，能力造成了重大的临床问题 伴随着大量的内皮细胞损失，最终 导致不可逆的角膜水肿。 目前，临床上角膜内皮的替代是通过 健康供体角膜的同种移植。 常规更换 然而，治疗对质量和治疗有一定的限制。 目前适合角膜移植术的供体角膜数量。 随着 最终目标是增加可用供体角膜的潜在库 为了移植的目的，我们提出了一组实验，旨在 增强/增强现有的供体角膜。 这些研究是补充 我们正在进行的内皮播种研究（其中有完整的 替换供体内皮单层），旨在 增加正常（合适）组织的内皮细胞密度和 低密度角膜，否则不适合穿透 角膜移植术。 除了通过以下方式增加组织供应的潜力之外 改善低密度供体角膜的质量，任何增加 内皮单层的细胞密度将提供更大的 穿透性角膜移植术后的内皮储备。 内皮细胞 穿透性角膜移植术后的损失显示出显着的一年细胞 损失33-45%。 这为未来留下了很少的内皮储备 穿透后对受损内皮的要求 角膜移植术。 我们提出的实验涉及添加 EGF 和/或 FGF 到细胞悬浮液中，以及现有单层细胞的增强 与外源细胞都是为了增加内皮细胞 角膜移植前的角膜密度。 这些结果的潜在人类应用具有深远的影响 临床意义。 更换损坏（患病）的 具有活细胞培养内皮细胞的内皮细胞（建立人类 冷冻保存的角膜内皮细胞库）以重新填充老化或 在穿透之前、期间或代替穿透时患病的角膜 角膜移植术将显着增加合适的角膜数量 对于移植，提供一种标准化已建立的方法 供体制剂的数量并提高安全性和成功率 未来的人类角膜移植手术。