Faculty of Pharmacy, Middle East University, Amman 11831, Jordan; Applied Science Research Center, Applied Science Private University, Amman 11152, Jordan.
Universidad Nacional de San Agustin de Arequipa, Arequipa, Peru.
Life Sci. 2023 Sep 15;329:121968. doi: 10.1016/j.lfs.2023.121968. Epub 2023 Jul 22.
Retinal ischemia/reperfusion (I/R) injury is a common pathological basis for various ophthalmic diseases. This study aimed to investigate the potential of sulforaphane (SFN) and Homer1a in regulating cell apoptosis induced by retinal I/R injury and to explore the underlying regulatory mechanism between them.
In in vivo experiments, C57BL/6J mice and Homer1/Homer1a/Nestin-Cre mice were used to construct retinal I/R injury models. In vitro experiments utilized the oxygen-glucose deprivation-reperfusion (OGD/R) injury model with primary retinal ganglion cells (RGCs). The effects of Homer1a and SFN on cell apoptosis were observed through pathological analyses, flow cytometry, and visual electrophysiological assessments.
We discovered that after OGD/R injury, apoptosis of RGCs and intracellular Ca activity significantly increased. However, these changes were reversed upon the addition of SFN, and similar observations were reproduced in in vivo studies. Furthermore, both in vivo and in vitro studies confirmed the upregulation of Homer1a after I/R, which could be further enhanced by the administration of SFN. Moreover, upregulation of Homer1a resulted in a reduction in cell apoptosis and pro-apoptotic proteins, while downregulation of Homer1a had the opposite effect. Flash visual evoked potential, oscillatory potentials, and escape latency measurements in mice supported these findings. Furthermore, the addition of SFN strengthened the neuroprotective effects in the OGD/R + H group but weakened them in Homer1/Homer1a/Nestin-Cre mice.
These results indicate that Homer1a plays a significant role in the therapeutic potential of sulforaphane for retinal I/R injury, thereby providing a theoretical basis for clinical treatment.
视网膜缺血/再灌注（I/R）损伤是多种眼病的常见病理基础。本研究旨在探讨萝卜硫素（SFN）和 Homer1a 对调控视网膜 I/R 损伤诱导的细胞凋亡的潜在作用，并探讨它们之间的潜在调控机制。
在体内实验中，使用 C57BL/6J 小鼠和 Homer1/Homer1a/Nestin-Cre 小鼠构建视网膜 I/R 损伤模型。在体外实验中，采用原代视网膜神经节细胞（RGCs）氧葡萄糖剥夺/再灌注（OGD/R）损伤模型。通过病理分析、流式细胞术和视觉电生理评估观察 Homer1a 和 SFN 对细胞凋亡的影响。
我们发现，在 OGD/R 损伤后，RGC 细胞凋亡和细胞内 Ca 活性显著增加。然而，这些变化在 SFN 加入后得到逆转，在体内研究中也得到了类似的观察结果。此外，体内和体外研究均证实 I/R 后 Homer1a 上调，SFN 的给药可进一步增强其上调。此外，Homer1a 的上调导致细胞凋亡和促凋亡蛋白减少，而下调 Homer1a 则产生相反的效果。在小鼠中进行闪光视觉诱发电位、振荡电位和逃避潜伏期测量支持了这些发现。此外，SFN 的加入增强了 OGD/R+H 组的神经保护作用，但在 Homer1/Homer1a/Nestin-Cre 小鼠中削弱了其作用。
这些结果表明，Homer1a 在萝卜硫素治疗视网膜 I/R 损伤的潜在作用中发挥重要作用，为临床治疗提供了理论依据。
