.png){kind=icon}
.png){kind=icon}
Return
APE1 deficiency drives lens epithelial cell senescence in age-related cataract formation
.png){kind=icon}
OA
AI
Q
Q
P
Y
X
X
D
D
M
H
T
C
DOI：10.1016/j.gendis.2026.102384.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Aging-related cataract (ARC), a leading cause of blindness worldwide, profoundly impairs visual function and quality of life in the elderly. Senescence of lens epithelial cells (LECs) is a major contributor to ARC, yet the molecular mechanisms underlying this process remain incompletely defined. To identify key regulators of LEC senescence, we investigated the role of apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional protein involved in both redox regulation and DNA repair. APE1 expression declined with age in human cataractous lenses, and its genetic ablation in mice resulted in spontaneous cataract formation. Functional suppression of APE1—via genetic knockdown, the redox inhibitor E3330, or the repair inhibitor APE1-IN-1—consistently accelerated LEC senescence. Mechanistically, inhibition of APE1 redox activity exacerbated ROS-induced mitochondrial dysfunction through the PI3K–AKT/p38 MAPK pathway, whereas impairment of APE1 repair activity reduced DHCR24 expression via DNMT1/TET3-mediated CpG hypermethylation. Consistently, APE1C64S/C64S and APE1E95A/E95A knock-in mouse models demonstrated that disruption of either APE1 function led to mitochondrial injury, DHCR24 hypermethylation, LEC senescence, and lens opacity in vivo. Together, these findings establish APE1 as a key protector against ARC by maintaining mitochondrial homeostasis and preventing pathogenic epigenetic alterations. Targeting APE1-related pathways may offer a promising strategy for early intervention in ARC.
Keywords:
Aging-related cataracts (ARC)
Apurinic endonuclease 1 (APE1)
Cellular senescence
DNA methylation
Mitochondrial dysfunction
Journal
G
IF:
9.4
Papers:
304
Citations:
0
Organization
Cited Papers