Poly(ADP-ribose) polymerase inhibitor PJ34 protects against UVA-induced oxidative damage in corneal endothelium

Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells. Poly (ADP-ribose) polymerase (PARP) was reported to be involved in cell death and apoptosis of several diseases. How...

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Published in:	Apoptosis (London) 2021-12, Vol.26 (11-12), p.600-611
Main Authors:	Wang, Xin, Dong, Chunxiao, Zhou, Qingjun, Duan, Haoyun, Zou, Dulei, Gong, Yajie, Ma, Bochao, Li, Zongyi, Shi, Weiyun
Format:	Article
Language:	eng
Subjects:	Animals Apoptosis Biochemistry Biomedical and Life Sciences Biomedicine Blindness Cancer Research Cell Biology Cell death Cornea Corneal dystrophy Dystrophy Edema Endothelial Cells Endothelium Endothelium, Corneal - metabolism Inhibitors Irradiation MAP kinase MAP kinase phosphatase Mice Mitochondria Oncology Oxidative Stress Phenanthrenes Phosphorylation Poly(ADP-ribose) Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase 1 Poly(ADP-ribose) Polymerase Inhibitors - metabolism Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Radiation damage Ribose Virology
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Summary:	Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells. Poly (ADP-ribose) polymerase (PARP) was reported to be involved in cell death and apoptosis of several diseases. However, the role of PARP1 in the progression of FECD remains elusive. In the present study, we reported that UVA irradiation caused the corneal endothelial damage and corneal edema in mice, which was accompanied with the elevated activity of PARP1 and PAR. The PARP1 inhibitor PJ34 resolved the corneal edema and protected corneal endothelium from UVA-induced oxidative damage, mitochondrial dysfunction, and cell apoptosis. Mechanistically, PARP1 inhibition exerted its anti-apoptotic effects through downregulation of the phosphorylation levels of JNK1/2 and p38 MAPK and subsequently the increase of MKP-1. Our results suggest that PARP1 inhibition protects corneal endothelium from UVA-induced oxidative damage, which provides a potential alternative strategy for the therapy of FECD.
ISSN:	1360-8185 1573-675X