CYR61/CCN1: A novel mediator of redox response in corneal stromal cells of keratoconus

作者：Xiaoxue Liu, Xiaowen Zhang, Qinghua Li, Chaoqun Wei, Xinghan Guo, Longfei Zhao, Ting Liu, Qingdong Bao, Shengqian Dou, Berthold Seitz, Hua Gao · 发表于：Experimental Eye Research · 年份：2024 · DOI：10.1016/j.exer.2024.110093 · 被引用次数：8 · 研究领域：Corneal surgery and disorders、Connective Tissue Growth Factor Research、Corneal Surgery and Treatments

Keratoconus (KC) is a progressive, multifactorial and ectatic corneal disorder that characterized by steepening thinning of the cornea. It was previously demonstrated that oxidative stress has a strong link with KC progression. However, the molecular mechanism underlying oxidative stress response in KC remains unclear. Hence, the present study analyzed the heterogeneity of response of corneal stromal cells (CSCs) to oxidative stress in order to further illustrate how oxidative shape the pathophysiology of KC. Single-cell transcriptomics analysis revealed that CSCs demonstrated significant higher oxidative stress score in the KC group compared to the Ctrl group. The expression of oxidative markers verified by experiments illustrated elevated oxidative stress levels and insufficient antioxidant levels in CSCs of KC. In further single-cell transcriptomics analysis, we identified CYR61 to distinguish different subgroups of CSCs responding to oxidative stress. The cornea stroma cells in KC could be differentiated into CYR61 high cells and CYR61 low cells. Of note, the CYR61 high cells showed lower score in collagen production process and higher score in collagen catabolic process. Further experiments illustrated that CYR61 was elevated in KC and associated with collagen production. • Keratoconus (KC) is the most common blinding eye disease in young adults. Oxidative stress has long been suspected to shape the pathophysiology of KC, however, the pathophysiology remains poorly under...