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Inhibition of PARP activity improves therapeutic effect of ARPE-19 transplantation in RCS rats through decreasing photoreceptor death
Journal article   Peer reviewed

Inhibition of PARP activity improves therapeutic effect of ARPE-19 transplantation in RCS rats through decreasing photoreceptor death

Furong Gao, Zongyi Li, Ziwei Kang, Dandan Liu, Peng Li, Qingjian Ou, Jing-Ying Xu, Weiye Li, Haibin Tian, Caixia Jin, …
Experimental eye research, v 204, 108448
Mar 2021
DOI: https://doi.org/10.1016/j.exer.2021.108448
PMID: 33484702
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

ARPE-19 cell Cell transplantation Combined treatment Photoreceptor Poly(ADP-Ribose) polymerase RCS rat Retinal degeneration Retinal pigment epithelium
Photoreceptor (PR) dysfunction or death is the key pathological change in retinal degeneration (RD). The death of PRs might be due to a primary change in PRs themselves or secondary to the dysfunction of the retinal pigment epithelium (RPE). Poly(ADP-ribose) polymerase (PARP) was reported to be involved in primary PR death, but whether it plays a role in PR death secondary to RPE dysfunction has not been determined. To clarify this question and develop a new therapeutic approach, we studied the changes in PAR/PARP in the RCS rat, a RD model, and tested the effect of PARP intervention when given alone or in combination with RPE cell transplantation. The results showed that poly(ADP-ribosyl)ation of proteins was increased in PRs undergoing secondary death in RCS rats, and this result was confirmed by the observation of similar changes in sodium iodate (SI)-induced secondary RD in SD rats. The increase in PAR/PARP was highly associated with increased apoptotic PRs and decreased visual function, as represented by lowered b-wave amplitudes on electroretinogram (ERG). Then, as we expected, when the RCS rats were treated with subretinal injection of the PARP inhibitor PJ34, the RD process was delayed. Furthermore, when PJ34 was given simultaneously with subretinal ARPE-19 cell transplantation, the therapeutic effects were significantly improved and lasted longer than those of ARPE-19 or PJ34 treatment alone. These results provide a potential new approach for treating RD. •Hyperactivated PARP is closely associated with secondary photoreceptor death caused by RPE dysfunction.•The PARP inhibitor PJ34 protects photoreceptors in RCS rats.•Simultaneous application with PJ34 improves the therapeutic effect of ARPE-19 transplantation in RCS rats.•Combining PARP inhibitor and RPE cells may be a promising approach to treat retinal degeneration caused by RPE dysfunction.

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Web of Science research areas
Ophthalmology
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