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

• Published in: Journal of translational medicine Vol. 22; no. 1; pp. 38 - 10
• Main Authors: Kwon, ChangHyuk, Cho, Wonjun, Choi, Sung Woo, Oh, Heeseung, Abd El-Aty, A M, Gecili, Ibrahim, Jeong, Ji Hoon, Jung, Tae Woo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09-01-2024; BioMed Central; BMC
• Subjects: Age; AMD; AMP-Activated Protein Kinases; Analysis; Antibiotics; Antibodies; Apoptosis; Autophagy; Care and treatment; Caspase 3; Cell culture; Cell viability; DEL-1; Diagnosis; Dosage and administration; Endoplasmic reticulum; Endothelium; Epithelial Cells; ER stress; Eye diseases; Health aspects; Human subjects; Humans; Laboratories; Macular degeneration; Macular Degeneration - therapy; Membranes; Monoclonal antibodies; Musculoskeletal system; Myokines; Neovascularization; Pathogenesis; Patient outcomes; Phosphorylation; Proteins; Retina; Retinal pigment epithelial cells; Retinal pigment epithelium; Retinal Pigments; siRNA; Software; Tunicamycin; Tunicamycin - pharmacology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Western blotting; South Korea; United States > US; Retinal pigment epithelial cells; AMD; ER stress; DEL-1; Autophagy; Apoptosis
• DOI: 10.1186/s12967-024-04858-9
• EISSN: 1479-5876

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.
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.
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.
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.