선택적 세로토닌 재흡수 억제제에 의한 망막색소상피세포의 자가포식 유도

Induction of Autophagy by Selective Serotonin Reuptake Inhibitors in Retinal Pigment Epithelial Cells

Dry age-related macular degeneration (AMD) is a disease characterized by the accumulation of drusen in the macula. N-retinylidene-N-retinylethanolamine (A2E) is a representative retinal accumulation product. After photooxidation by blue light in the retina, A2E inhibits autophagy and causes toxicity such as inflammation, lipid peroxidation, destruction of mitochondrial function, and activation of the complement system. Here, we investigated the effect of selective serotonin reuptake inhibitors on autophagy in retinal pigment epithelial cells. Citalopram, fluvoxamine, escitalopram, paroxetine, sertraline, and fluoxetine induced the formation of LC3-II and phosphorylation of p62 in ARPE-19 cells. In addition, these compounds improved autophagic flux monitored by bafilomycin A1 assay. Furthermore, citalopram and fluvoxamine reduced cellular A2E levels in ARPE-19 cells. These results suggest that SSRIs may have the potential to prevent dry AMD, not only by inducing autophagy but also by promoting the removal of A2E in the retina.