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Murilo F Roggia, Yasuo Noda, Tomoyasu Shiraya, Takashi Ueta; Protective Effect of Photoreceptor Outer Segments Phagocytosis for Retinal Pigment Epithelial Cells by PGC-1α/SIRT1. Invest. Ophthalmol. Vis. Sci. 2014;55(13):372.
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Aging process is accepted to present an association with different diseases affecting the retinal pigment epithelial cells (RPE). Both peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and sirtuin 1 (SIRT1) are considered as important regulators of metabolism and physiological aging phenomenon. The objective of this study was to evaluate the role of photoreceptor outer segments (POS) phagocytosis in aging signaling in RPE cells.
Human RPE cells (ARPE-19) were treated with POS isolated from porcine eyes for 3-9 hours. Different concentrations of POS were used. Both PGC-1α and SIRT1 mRNA and protein expression were measured before and after treatment with POS. Expressions of antioxidant enzymes and senescence was analyzed. Mitochondrial biogenesis was evaluated by measuring the mitochondrial DNA replication. Knockdown of PGC-1α and SIRT1 in RPE cells was analyzed.
First, we observed the knockdown of PGC-1α or SIRT1 by small interfering RNAs resulted in decreased expression of anti-oxidant enzymes and increased expression of senescence markers in RPE cells, confirming the involvement of these molecules in aging signaling in RPE. When treated with POS, a dose-dependent elevation in the expression of PGC-1α and SIRT1 was observed in RPE cells while the treatment with latex beads did not change the expression. Consistently, expression of anti-oxidant enzymes was upregulated and expression of senescence markers was downregulated in RPE cells phagocytosing POS. Furthermore, mitochondrial biogenesis was induced by POS in RPE cells shown by the increased mitochondrial DNA replication and the expression of prohibitin, a mitochondrial marker protein.
Our data indicates that one of the physiological roles of POS phagocytosis for RPE cells might be the regulation of PGC-1α/SIRT1 pathway that leads to mitochondrial biogenesis and expression of anti-oxidant enzymes, as well as the downregulation of senescence markers.
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