DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells


Kwon C., Cho W., Choi S. W., Oh H., HASSIBELNABY A. M. A., Gecili I., ...More

Journal of Translational Medicine, vol.22, no.1, 2024 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 22 Issue: 1
  • Publication Date: 2024
  • Doi Number: 10.1186/s12967-024-04858-9
  • Journal Name: Journal of Translational Medicine
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Biotechnology Research Abstracts, CINAHL, MEDLINE, Directory of Open Access Journals
  • Keywords: AMD, Apoptosis, Autophagy, DEL-1, ER stress, Retinal pigment epithelial cells
  • Ataturk University Affiliated: Yes

Abstract

Background: Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells. Methods: We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining. Results: Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor. Conclusions: Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.