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一种仅通过工程化成纤维细胞生长因子 1 刺激加速愈合的人角膜去表皮化器官培养模型。

A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1.

机构信息

Trefoil Therapeutics, Inc.;

Trefoil Therapeutics, Inc.

出版信息

J Vis Exp. 2022 Jul 22(185). doi: 10.3791/63482.

DOI:10.3791/63482
PMID:35938798
Abstract

Fuchs Endothelial Corneal Dystrophy (FECD) results from dysfunctional corneal endothelial cells (CECs) and is currently treated by transplantation of the whole cornea or Descemet's membrane. Recent developments in ocular surgery have established Descemet's Stripping Only (DSO), a surgical technique in which a central circle of guttae-dense Descemet's membrane is removed to allow for the migration of CECs onto the smooth stroma, restoring function and vision to the cornea. While this potential treatment option is of high interest in the field of ophthalmic research, no successful ex vivo models of DSO have been established and clinical data is limited. This work presents a novel wound-healing model simulating DSO in human donor corneas. Using this approach to evaluate the efficacy of the human engineered FGF1 (NM141), we found that treatment accelerated healing via stimulation of migration and proliferation of CECs. This finding was confirmed in 11 pairs of human corneas with signs of dystrophy reported by the eye banks in order to verify that these results can be replicated in patients with Fuchs' Dystrophy, as the target population of the DSO procedure.

摘要

Fuchs 内皮角膜营养不良(FECD)是由角膜内皮细胞(CEC)功能障碍引起的,目前可通过全角膜或 Descemet 膜移植进行治疗。最近眼科学领域的发展确立了仅撕除 Descemet 膜(DSO)手术,这是一种通过去除中央密集的 Descemet 膜的圆形区域来允许 CEC 迁移到光滑的基质上的手术技术,从而恢复角膜的功能和视力。虽然这种潜在的治疗选择在眼科研究领域引起了极大的兴趣,但尚未建立成功的 DSO 体外模型,临床数据也有限。本研究提出了一种模拟人供体角膜 DSO 的新型伤口愈合模型。使用这种方法来评估人源工程 FGF1(NM141)的疗效,我们发现治疗通过刺激 CEC 的迁移和增殖来加速愈合。为了验证这些结果可以复制到 Fuchs 营养不良患者中,作为 DSO 手术的目标人群,我们在 11 对有报道的角膜营养不良迹象的人眼角膜上进行了这项研究。

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