MODULATION OF THE SENESCENCE ASSOCIATED SECRETORY PHENOTYPE IN RETINAL PIGMENT EPITHELIAL CELLS

SUBURO AM; WEIL B; MARQUIONI-RAMELLA MD; MARQUIONI-RAMELLA MD; MARAZITA MC; MARAZITA MC; TATE P; TATE P; SUBURO AM; WEIL B

Congreso; Congreso Conjunto de Sociedades de Biociencias; 2017

Cellular senescence triggers the expression of a wide variety of inflammatory factors named the senescence associated secretory phenotype (SASP). The SASP may contribute to diseases of aging by disrupting tissue structure and function. Our previous findings support the hypothesis that cell senescence of the retinal pigment epithelium (RPE) plays a role in the pathogenesis of Age-related macular degeneration (AMD). Thus, we have reported that oxidative-stress induced senescence in RPE cells dysregulates the expression of factors linked to AMD progression. We now hypoth- esized that polyphenols can block the senescent secretome by modulating inflammatory signaling pathways. Aims: To evaluate the effect of Caffeic acid (CAF) on SASP expression and its paracrine effects. Methods: Human RPE cells (ARPE-19 line) were incubated with 150 μM H2O2 for 90 minutes during 3 days (d), and then maintained for 9 d to establish senescent cultures (SEN). These cultures were exposed to 6 μg/ml of CAF for the last 6 d. mRNA and protein levels for IL1b, IL8, IL6 were analyzed by qPCR or western blot. Senescence was deter- mined by positive staining for Senescence Associated βgal activity and increased expression of p21 and p16. gH2AX was tested by IFI. Results: SEN cultures expressed high levels of IL1b and IL8, which were reduced by CAF treatment (p