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

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

  • Life Sci. 2023 Jul 22;121968. doi: 10.1016/j.lfs.2023.121968.
Mohamed J Saadh 1,  Roxana Yolanda Castillo-Acobo 2,  Hala Baher 3,  Jayasankar Narayanan 4,  Jessica Paola Palacios Garay 5,  Michelle Naomi Vera Yamaguchi 6,  José Luis Arias Gonzáles 7,  Juan Carlos Cotrina-Aliaga 8,  Shaik Vaseem Akram 9,  Natrayan Lakshmaiya 10,  Ali H Amin 11,  Mohamed Mohany 12,  Salim S Al-Rejaie 12,  Muhammad Ahsan 13,  Abolfazl Bahrami 14,  Reza Akhavan-Sigari 15
Affiliations

Affiliations

  • 1 Faculty of Pharmacy, Middle East University, Amman 11831, Jordan; Applied Science Research Center, Applied Science Private University, Amman 11152, Jordan.
  • 2 Universidad Nacional de San Agustin de Arequipa, Arequipa, Peru.
  • 3 Department of Radiology and Ultrasonography Techniques, College of Medical Techniques, Al-Farahidi University, Baghdad, Iraq.
  • 4 Department of Pharmacology, SRM College of Pharmacy, SRMIST, Tamil Nadu, India.
  • 5 Universidad Nacional Mayor de San Marcos, Lima, Peru.
  • 6 Universidad de San Martín de Porres, Lima, Peru.
  • 7 Department of Social Sciences, Faculty of Social Studies, University of British Columbia, BC, Canada.
  • 8 Universidad Privada San Juan Bautista, Chincha, Peru.
  • 9 Uttaranchal Institute of Technology, Division of research and Innovation, Uttaranchal University, Dehradun, India.
  • 10 Department of Mechanical Engineering, Saveetha School of Engineering, SIMATS, Chennai, Tamil Nadu, India.
  • 11 Zoology Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt.
  • 12 Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
  • 13 Department of Measurements and Control Systems, Silesian University of Technology, Gliwice, Poland; Joint Doctoral School, Silesian University of Technology, Akademicka 2A, Gliwice, Poland. Electronic address: Muhammad.Ahsan@polsl.pl.
  • 14 Department of Cell Biology, Tuebingen University, Tuebingen, Germany. Electronic address: A.Bahrami@ut.ac.ir.
  • 15 Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw, Poland; Department of Neurosurgery, University Medical Center Tuebingen, Germany.
PMID: 37487941 DOI: 10.1016/j.lfs.2023.121968
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.

Keywords

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

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