Research Paper Volume 10, Issue 11 pp 3474—3485
TGF-β induces corneal endothelial senescence via increase of mitochondrial reactive oxygen species in chronic corneal allograft failure
- 1 Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
- 2 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
- 3 Department of Clinical Pharmacy, Affiliated Hospital of Qingdao University, Qingdao, China
- 4 Department of Child Health Care, Affiliated Hospital of Qingdao University, Qingdao, China
Received: July 25, 2018 Accepted: November 15, 2018 Published: November 28, 2018
https://doi.org/10.18632/aging.101659How to Cite
Abstract
The corneal endothelium (CE) dysfunction impairs optical transparency and leads to corneal allograft failure. Morphologically, CE cells are characterized by premature senescence at the late stage of corneal graft. However, the detailed molecular mechanisms are largely unknown. Here we found that transforming growth factor-β (TGF-β) is elevated in the CE of late graft failure. In addition, senescence-associated gene p21 and p16 are increased as well, which is consistent with their elevation upon TGF-β treatment in human corneal endothelial cell B4G12. Furthermore, TGF-β treatment leads to high positive ratio of SA-β-gal, indicating B4G12 cells undergo cellular senescence. Mechanistically, we demonstrated that TGF-β could induce mitochondrial ROS (mtROS) production and mtROS scavenger could rescue CE cell senescence upon TGF-β treatment. Our study provides new evidence that elevated TGF-β plays a crucial role in the CE cell senescence and loss in chronic corneal graft failure, which could be potential targets for clinical treatment.