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S. C. Maloney, J. Isenberg, P. Logan, S. Di Cesare, M. Young, M. N. Burnier, Jr.; Resveratrol Induces Proliferation of Mouse Retinal Progenitor Cells in a Dose-Dependent Manner. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3558.
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Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a phytoalexin and potent antioxidant found in red grapes and wine. It has been shown to have vast pharmacological effects depending on cell type, state and treatment dosage. Previous studies have demonstrated the neuroprotective effects of resveratrol in neurodegenerative diseases, including Alzheimer’s, Huntington’s and Parkinson’s. Accordingly, resveratrol may confer neuroprotection in retinal degenerative diseases such as retinitis pigmentosa. The purpose of this study was to investigate the effects of resveratrol on proliferation of isolated mouse retinal progenitor cells.
Retinal progenitor cells (RPCs) were isolated from post-natal day 1 (P1) green fluorescent protein (GFP) transgenic C57BL/6 mice and expanded in culture. Cells from passage 10 were used in this study. Cells were passed through a 40µm strainer, counted and seeded in a 96-well plate at a density of 4000 cells per well in 100µl of Neurobasal media with various concentrations of resveratrol: 1µM, 10µM, 50µM, 100µM, 200µM, 400µM, 600µM, 800µM, or 1mM. Eight wells were assayed for each resveratrol dosage. Cells in Neurobasal media without resveratrol were used as a control. An MTT assay was performed to assess cell proliferation after 48 hours of incubation. The assay was repeated twice to confirm results.
A dose-dependent increase in proliferation was observed with increasing concentrations of resveratrol beyond 50µM. There was a significant decrease in proliferation (p<0.05) with the 1µM and 10µM doses and no significant change with the 50µM dose with respect to the control. Beyond the 50µM dose, there was a statistically significant increase in proliferation (p<0.05) with each successive concentration up to and including the 1mM dose.
The observed dose-dependent effect of resveratrol on proliferation of mouse RPCs is a novel finding that warrants further investigation. Resveratrol is known to increase the activity of SIRT1, a deacetylase that affects major cell cycle regulators including NFkB and p53. Future studies will assess the effects of resveratrol on the expression of SIRT1 and other cell cycle modulating proteins in both differentiated and undifferentiated mouse RPCs.
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