The Senescence Difference Between the Central and Peripheral Cornea Induced by Sutures
Abstract Introduction: Cell senescence plays a regulatory role in tissue fibrosis, and corneal scarring is usually more severe in the central cornea based on clinical observation. We attempted to explore the senescence difference between the central and peripheral cornea in an in vivo mouse model of suture-induced senescence and an in vitro model of senescence with hydrogen peroxide (H2O2)-induced rabbit corneal fibroblasts. Methods: Male Balb/c mice (6-8 weeks) received sutures in the central, superior, inferior, nasal, and temporal cornea, and the sutures were removed on day 14. Corneal neovascularization (CNV) was observed under a slit lamp microscope with a digital camera. Fibroblasts isolated from central and peripheral rabbit corneas were induced with H2O2 to establish an in vitro model of senescence. The senescence was evaluated with SA-β-gal staining and gene expression analysis of p21, p27, and p53. Results: Senescent cells accumulated in the corneal stroma from day 3 to day 14 after the operation and peaked on day 14, later than CNV. More senescent keratocytes were observed in the peripheral cornea in the mouse model. The peripheral corneal fibroblasts were more likely to become senescent related to H2O2 in vitro. The PCR results revealed that the senescence-related genes, p21, p27, and p53, were all highly expressed in the peripheral corneal fibroblasts. Conclusions: As senescent fibroblasts can limit tissue fibrosis, the senescence difference between the central and peripheral cornea may contribute to the difference in scarring.