The protective role of sulforaphane and Homer1a in retinal ischemia-reperfusion injury: Unraveling the neuroprotective interplay

Mohamed J. Saadh, Roxana Yolanda Castillo-Acobo, Hala Baher, Jayasankar Narayanan, Jessica Paola Palacios Garay, Michelle Naomi Vera Yamaguchi, José Luis Arias-Gonzáles, Juan Carlos Cotrina-Aliaga, Shaik Vaseem Akram, Natrayan Lakshmaiya, Ali H. Amin, Mohamed Mohany, Salim S. Al-Rejaie, Muhammad Ahsan, Abolfazl Bahrami, Reza Akhavan-Sigari

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: 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. Materials and methods: In in vivo experiments, C57BL/6J mice and Homer1flox/−/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. Key findings: We discovered that after OGD/R injury, apoptosis of RGCs and intracellular Ca2+ 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 Homer1flox/−/Homer1a+/−/Nestin-Cre+/− mice. Significance: 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.

Original languageEnglish
Article number121968
JournalLife Sciences
Volume329
DOIs
StatePublished - 15 Sep 2023

Bibliographical note

Publisher Copyright:
© 2023

Keywords

  • Homer1a
  • Oxygen-glucose deprivation-reperfusion
  • Retinal ganglion cells
  • Retinal ischemia-reperfusion injury
  • Sulforaphane

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