State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Transl Vis Sci Technol. 2022 Jun 1;11(6):28. doi: 10.1167/tvst.11.6.28.
Wound healing of the corneal epithelium mainly involves two types of cells: limbal stem/progenitor cells (LSCs) and differentiated central corneal epithelial cells (CECs). The healing ability of CECs is still debatable, and its correlated transcriptomic alterations during wound healing are yet to be elucidated. This study aimed to determine the healing ability and mechanisms underlying the actions of CECs using rabbit ocular surface injury models.
A central corneal ring-like residual epithelium model was used to investigate the healing ability of CECs. Uninjured and injury-stimulated LSCs and CECs were collected for transcriptomic analysis. The analysis results were verified by quantitative reverse transcriptase polymerase chain reaction, immunofluorescence staining, and two types of rabbit corneal injury models.
During wound healing, the upregulated genes in LSCs were mostly enriched in the mitotic cell cycle-related processes, but those in CECs were mostly enriched in cell adhesion and migration. CECs could repair the epithelial defects successfully at one-time injuries. However, after repetitive injuries, the CECs repaired notably slower and failed to completely heal the defect, but the LSCs repaired even faster than the one-time injury.
Our results indicated rabbit CECs repair the epithelial defect mainly depending on migration and its proliferative ability is limited, and LSCs are the main source of regenerative epithelial cells.
This study provides information on gene expression in the corneal epithelium during wound healing, indicating that regulation of the cell cycle, cell adhesion, and migration may be the basis for future treatment strategies for corneal wound healing.
角膜上皮的愈合主要涉及两种细胞:缘干细胞/祖细胞(LSCs)和分化的中央角膜上皮细胞(CECs)。CECs 的愈合能力仍存在争议,其在伤口愈合过程中相关的转录组变化尚待阐明。本研究旨在使用兔眼表面损伤模型来确定 CECs 的愈合能力及其作用机制。
使用中央角膜环状残留上皮模型来研究 CECs 的愈合能力。收集未受伤和受伤刺激的 LSCs 和 CECs 进行转录组分析。通过定量逆转录聚合酶链反应、免疫荧光染色和两种类型的兔角膜损伤模型对分析结果进行验证。
在伤口愈合过程中,LSCs 中上调的基因主要富集在有丝分裂细胞周期相关过程中,而 CECs 中上调的基因主要富集在细胞黏附和迁移中。CECs 可以一次性成功修复上皮缺陷。然而,在重复损伤后,CECs 的修复明显较慢,无法完全愈合缺陷,但 LSCs 的修复速度甚至比一次性损伤更快。
我们的结果表明,兔 CECs 主要通过迁移来修复上皮缺陷,其增殖能力有限,而 LSCs 是再生上皮细胞的主要来源。
Wang L, et al. Cornea. 2023;42(3):282-290. doi:10.1097/ICO.0000000000003602.