Department of Ophthalmology, Anhui Provincial Hospital, Anhui Medical University , Hefei, Anhui, China.
Department of Ophthalmology, Eye Center, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui, China.
Curr Eye Res. 2021 Jan;46(1):115-121. doi: 10.1080/02713683.2020.1776881. Epub 2020 Jun 15.
Our previous study discoveredreactive oxygen species (ROS) and apoptosis inducing factor (AIF) increased after retinal detachment. Parthanatos is a cell death form involving ROS and AIF, which is induced by poly (ADP-ribose) polymerase-1 (PARP-1). Therefore, we investigated whether PJ34 (a PARP-1 inhibitor) could inhibit parthanatos and protect the photoreceptors from cell death after retinal detachment (RD).
Experimental retinal detachment modelswere created in Sprague-Dawley rats by subretinal injection of sodium hyaluronate.PJ34 orDMSO were introduced into subretinal space at RD induction, respectively. The structure of retinas and the morphology of photoreceptors were observed by hematoxylin eosin (H&E) staining and transmission electron microscope (TEM). Parthanatos related proteins (PARP-1, PAR,AIF) were detected by Western blot. The vision-dependent behavior of rat was tested by Morris water maze.
H&E staining and TEM results indicated that the structure and outer nuclear layer (ONL) thickness of retinas were preserved, and the photoreceptors death decreasedwith PJ34 treatment. Western blot showed that the expression of PARP-1, PAR and AIF were decreased withPJ34 treatment. In addition, administration of PJ34 also improved the vision-dependent behavior of rat.
These findings suggested that PJ34 is a potential therapeutic agent that attenuated photoreceptor parthanatos death in retinal detachment through inhibition of PARP-1/AIF pathway.
我们之前的研究发现，视网膜脱离后活性氧（ROS）和凋亡诱导因子（AIF）增加。细胞坏死形式的 PARthanatos 涉及 ROS 和 AIF，其由聚（ADP-核糖）聚合酶-1（PARP-1）诱导。因此，我们研究了 PARP-1 抑制剂 PJ34 是否可以抑制 PARthanatos 并防止视网膜脱离（RD）后光感受器细胞死亡。
通过玻璃体内注射透明质酸钠在 Sprague-Dawley 大鼠中创建实验性视网膜脱离模型。在 RD 诱导时分别将 PJ34 或 DMSO 引入玻璃体内。通过苏木精-伊红（H&E）染色和透射电子显微镜（TEM）观察视网膜结构和光感受器形态。通过 Western blot 检测 PARthanatos 相关蛋白（PARP-1、PAR、AIF）。通过 Morris 水迷宫测试大鼠的视觉相关行为。
H&E 染色和 TEM 结果表明，视网膜的结构和外核层（ONL）厚度得以保留，并且光感受器死亡减少了 PJ34 处理。Western blot 显示，PJ34 处理后 PARP-1、PAR 和 AIF 的表达减少。此外，PJ34 的给药也改善了大鼠的视觉相关行为。
这些发现表明，PJ34 是一种潜在的治疗药物，通过抑制 PARP-1/AIF 通路减轻视网膜脱离中的光感受器 PARthanatos 死亡。
