Descemet\u2019s Membrane Supports Corneal Endothelial Cell Regeneration in Rabbits

Jingyao Chen,Dulei Zou,Xin He,Liying Zhang,Zuguo Liu,Shu Yang,Xian Li,Yanzi Wang,Ying-Ting Zhu,Yongxiong Chen,Zhiyuan Li,Qianqian Hu,Huimin Sun,Shangkun Ou,Changkai Jia,Juan Li,Scheffer C G Tseng,Junqi Wang,Wei Li

doi:10.1038/s41598-017-07557-2

Abstract

Descemet’s membrane (DM) helps maintain phenotype and function of corneal endothelial cells under physiological conditions, while little is known about the function of DM in corneal endothelial wound healing process. In the current study, we performed in vivo rabbit corneal endothelial cell (CEC) injury via CEC scraping, in which DM remained intact after CECs removal, or via DM stripping, in which DM was removed together with CECs. We found rabbit corneas in the CEC scraping group healed with transparency restoration, while there was posterior fibrosis tissue formation in the corneas after DM stripping on day 14. Following CEC scraping on day 3, cells that had migrated toward the central cornea underwent a transient fibrotic endothelial-mesenchymal transition (EMT) which was reversed back to an endothelial phenotype on day 14. However, in the corneas injured via DM stripping, most of the cells in the posterior fibrosis tissue did not originate from the corneal endothelium, and they maintained fibroblastic phenotype on day 14. We concluded that corneal endothelial wound healing in rabbits has different outcomes depending upon the presence or absence of Descemet’s membrane. Descemet’s membrane supports corneal endothelial cell regeneration in rabbits after endothelial injury.

Highlights

Mechanical scrape injury[10] and the transcorneal freeze injury[2, 11] models are commonly used to characterize endothelial wound healing biology
We compared the rabbit corneal endothelial wound healing responses induced by Descemet’s membrane (DM) stripping and the corneal endothelial cell (CEC) scraping method to determine the contribution made by the DM to restoring corneal deturgescence and transparency
Endothelial cells outside the stripping line remained the regular shape, while there was no cell present inside the stripping line, as well as the central cornea after DM stripping (Fig. 1F). These results proved that both CEC scraping and DM stripping method successfully created corneal endothelial wounding model, and there was no endothelial cell remained in the wounding area

Summary

Introduction

Mechanical scrape injury[10] and the transcorneal freeze injury[2, 11] models are commonly used to characterize endothelial wound healing biology. The wound healing process includes CEC migration, elongation, coalescence, and mitosis procedures[14] Despite these behavioral changes, the endothelial cells maintain a normal phenotype[10]. It was suggested that this corneal endothelial fibrogenic response is caused by endothelial mesenchymal transition (EMT) activation leading to myofibroblast transdifferentiation[22, 23] In these two endothelial injury models, Descemet’s membrane (DM) maintained intact[10]. DM is synthesized by corneal endothelial cells during both the prenatal and postnatal periods of life[31], and thickens with age[32] It contributes to maintaining the CEC phenotype and function under physiological conditions[33, 34]. Our results indicate that DM plays a critical role in corneal endothelial cell regeneration and function restoration in rabbits

Methods

Results

Conclusion