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Y. Chen, J. Cai, P. Sternberg; Mammalian Target of Rapamycin Signaling in Regulation of Aging of Human RPE. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4181.
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Mammalian target of rapamycin (mTOR) is an important sensor of growth factors and nutrients; and regulates cell growth and proliferation. The mTOR controls the process of aging, which is a well-defined risk factor of atrophic AMD. The purposes of this study were to characterize the mTOR signaling network in cultured human retinal pigmental epithelium (RPE) cells and to explore its potential roles in RPE aging.
Primary human RPE cells and an immortalized ARPE-19 cell line were used for the study. The expression of major components of mTOR pathways were detected by RT-PCR and Western blot analyses. Formation of the two mTOR signaling complexes, mTORC1 and mTORC2, were determined by co-immunoprecipitation. The mTORC1 activity was assessed by measuring the phosphorylation status of its downstream effector proteins. The in vitro aging of human RPE was determined by measuring the senescence associated β-galactosidase activity.
The mTOR pathway responded to various upstream stimuli in a rapamycin-sensitive manner. FKBP8, a newly identified endogenous mTOR inhibitor, exerted its inhibitory functions on mTOR signaling in the RPE. The prototypic mTOR inhibitor Rapamycin 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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