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Michael R Kozlowski, K. Elizabeth Bond, Mandana Nasiri Manesh, ; Inhibition of Senescence in RPE Cells by Astragaloside IV: Implications for Treating AMD. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):178.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study is to assess the potential utility of astragaloside IV (AG4) in treating age-related macular degeneration (AMD). A growing body of evidence suggests that senescence of the retinal pigment epithelial (RPE) cells contributes to the pathology of AMD. One of the primary triggers of senescence in many types of cells is critical shortening of chromosomal telomeres. This can be produced either by erosion during a large number of cell divisions, or by breakage through oxidative damage. AG4 has been reported to reduce the number of critically short telomeres and to attenuate the effects of senescence in other systems. The present study was undertaken to determine whether AG4 also attenuates the signs of senescence in RPE cells.
The ARPE-19 human RPE cell line was used to model RPE cells. Signs of senescence were induced in ARPE-19 cultures either by growing them through a large number of cell divisions or by exposing them to an oxidizing agent (tert-butyl hydroperoxide; tBHP). The occurrence of senescence was monitored by staining the cultures for senescence-associated beta-galactosidase (SABG) activity and counting the percentage of cells that stained positively. Cultures were treated with either AG4 or its vehicle while growing to senescence, or before and after treatment with tBPH.
ARPE-19 cells that had sustained the number of cell divisions at which senescent signs normally appear (55-79) displayed fewer SABG-stained cells if they had been grown in the presence of AG4 than if they had been grown in the presence of its vehicle. AG4 also inhibited another sign of senescence: a transient decrease in cell viability. Likewise, ARPE-19 cultures that had been treated with tBHP contained fewer SABG-stained cells if they had been treated with AG4 before and after the tBHP exposure.
AG4 reduced the signs of senescence in ARPE-19 cells, as it has also been reported to do in other systems. This reduction occurred whether senescence was induced by multiple rounds of cell division or through treatment with an oxidizing agent. This is significant since oxidative damage may be a major pathway to cell senescence in the retina. The ability of AG4 to reduce senescence in RPE cells suggests that it, or compounds with like activity, may be useful in treating AMD.
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