Research progress in autologous regeneration of human corneal endothelial cells
CHEN Jin,, FU Yao,
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
Human corneal endothelial cells (HCECs) are very important for maintaining corneal transparency, but HCECs remain arrested at the G1 phase after embryonic development and could not proliferate and regenerate in vivo. The density of HCECs decreases spontaneously with corneal development and aging, while systemic factors and corneal diseases can further cause a massive loss to HCECs, lead to corneal opacity and edema and ultimately induce vision impairment. Therefore, the regeneration of HCECs has always been a heated topic in the field of corneal endothelial research. Currently, function restoration of exogenous corneal endothelium mediated by cell therapy and autologous regeneration of endogenous HCECs have made amazing breakthroughs, with endogenous HCECs autologous regeneration being a more convenient and physiological treatment option. This review summarizes and analyzes the strategies and related techniques that are currently applied to the autologous regeneration of HCECs in aspects of operative treatment, gene therapy and pharmacological treatment.
CHEN Jin, FU Yao. Research progress in autologous regeneration of human corneal endothelial cells. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2023, 43(6): 775-780 doi:10.3969/j.issn.1674-8115.2023.06.015
相对于手术治疗和基因治疗，药物治疗是一种更为便捷的途径。一方面该治疗可以局部给药的方式避免可能出现的全身并发症或手术相关并发症，另一方面在治疗时可实时观察效果，若无效则可及时采取其他补救措施。目前，研究较为广泛的药物为生长因子及Rho相关蛋白激酶（Rho-associated protein kinase，ROCK）抑制剂［1］。此外，研究人员还针对FECD的病理特征［如HCECs发生内皮-间质转化（endothelial-to-mesenchymal transition，EndMT）、氧化应激的增加导致HCECs凋亡等］，利用TGF-β抑制剂、抗氧化剂来发挥治疗作用。
TGF-β具有广泛的生物学功能，如参与细胞生长及分化、创伤修复、机体免疫、调节基质合成等。HCECs表面可同时表达TGF-β的3种受体，且房水中的TGF-β与HCECs自身合成的TGF-β均可对HCECs产生重要的影响［33-34］。研究［35］发现，在兔角膜内皮细胞中，TGF-β能够降低细胞周期蛋白依赖性激酶4（cyclin-dependent protein kinase，CDK4）的表达，从而阻止兔角膜内皮细胞进入S期，干扰其细胞周期的进展。此外，TGF-β还可刺激内皮细胞发生EndMT［36］。有研究［37-38］显示，在体外TGF-β信号通路抑制剂4-［4-（1, 3-苯并二氧戊环-5-基）-5-（2-吡啶基）-1H-咪唑-2-基］苯甲酰胺（SB431542）可促进细胞的增殖并降低EndMT的发生。基于上述研究我们发现，TGF-β作为普遍存在的多功能细胞因子，可参与机体的众多生理过程；且TGF-β信号通路抑制剂具有一定的治疗潜力，但尚缺少临床研究，使用时需慎重考量。
CHEN Jin drafted the original manuscript. FU Yao conceived the idea and participated in the reviewing and editing. Both authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
COMPETING INTERESTS
All authors disclose no relevant conflict of interests.
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