Abstract
Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.
Highlights
Age-related macular degeneration (AMD) is a progressive neurodegenerative condition and the leading cause of blurry vision and blindness in the elderly population of industrialized nations
To determine whether quercetin is toxic to ARPE-19 cells, we exposed them to various concentrations of quercetin and evaluated the cell viability
We determined the viability of ARPE-19 cells, which were treated with various concentrations of quercetin (1.25, 2.5, and 5 μM) and 6 mM NaIO3 (Figure 1B)
Summary
Age-related macular degeneration (AMD) is a progressive neurodegenerative condition and the leading cause of blurry vision and blindness in the elderly population of industrialized nations. The primary treatment for wet AMD is the administration of antivascular endothelial growth factor, but at present, no effective treatment strategies exist for dry AMD. B (AKT) signaling pathways [23] They found that cytosolic ROS-dependent p38 and JNK activation led to the death of NaIO3 -treated ARPE-19 cells (human retinal pigment epithelial cells), whereas cytosolic ROS-mediated autophagy and mitochondrial dynamic balance contributed to cell survival. Their data suggested that ROS, AKT, and ERK signaling pathways played a role in pentraxin 3 ( known as the tumor necrosis factor-α-stimulated gene) production in response to NaIO3 in ARPE-19 cells. 3-kinase (PI3K) expression and downstream signaling molecules and the NaIO3 -induced regulation of ROS and apoptotic proteins in ARPE-19 cells and AMD animal models have not yet been determined
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