Abstract
Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.
Highlights
Age-related macular degeneration (AMD), a multifaceted disease with demographic, environmental, and genetic risk factors, is among the most common causes of irreversible blindness in the world [1,2,3]
Oxidative stress was generated by the addition of various concentrations of H2 O2 for 24 h and cell viability was measured via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
ARPE-19 cells treated with H2 O2 underwent apoptosis through both the intrinsic and extrinsic pathways in response to cellular damage to the DNA, mitochondria, and Endoplasmic Reticulum (ER)
Summary
Age-related macular degeneration (AMD), a multifaceted disease with demographic, environmental, and genetic risk factors, is among the most common causes of irreversible blindness in the world [1,2,3]. AMD progression occurs over an extended time period and its incidence rapidly increases in patients over 70 years old [1,4]. There are two major types of AMD: exudative or “wet” and non-exudative or “dry” [1,5]. AMD have the “dry” form of the disease; the “dry” form is characterized by lipofuscin accumulation in the retinal pigment epithelial (RPE) cells and drusen formation beneath the RPE cells in Bruch’s membrane. In patients with “dry” AMD, these alterations of the normal retinal architecture lead to significant functional limitations but not loss of central vision [1,5]. “wet” AMD comprises approximately 10–15% of all AMD cases and features choroidal neovascularization and abnormal blood vessel formation in macula
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