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Y. Chen, J. Cai, P. Sternberg, Jr.; Altered mTOR Signaling in Senescent Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6173.
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Mammalian target of rapamycin (mTOR)-mediated signaling network is a central pathway controlling the process of aging, which is a well-defined risk factor of degenerative diseases such as atrophic age-related macular degeneration (AMD). The purposes of this study were to characterize the changes in mTOR pathway in senescent human retinal pigmental epithelium (RPE) cells.
Replicative senescence and post-confluent culture of primary human fetal RPE cells were used to induce in vitro aging. Senescence of the RPE was assessed by measuring the population doubling time, the activity of senescence associated β-galactosidase and the expression level of p16, a cyclin-dependent kinase inhibitor. Immortalized ARPE-19 cell line was used as a negative control for the study. Activation of mTOR complex I (mTORC1) was measured by the phosphorylation status of its downstream substrate S6.
The mTORC1 in RPE cells can be activated by nutrient and growth factor stimuli. Increased phosphorylation of S6 in response to amino acid was observed in aged RPE cells in two independent models of in vitro aging. Rapamycin, the prototypic mTOR inhibitor, inhibited the senescent phenotype of cultured human RPE cells.
RPE cells have functional mTOR signaling network. Delaying aging of the RPE by regulating mTOR signaling can be a potential therapeutic option for degenerative changes associated with atrophic AMD.
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