Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium

Sci Signal. 2018 May 29;11(532):eaag3315. doi: 10.1126/scisignal.aag3315.


The retinal pigment epithelium (RPE) transports nutrients and metabolites between the microvascular bed that maintains the outer retina and photoreceptor neurons. The RPE removes photoreceptor outer segments (POS) by receptor-mediated phagocytosis, a process that peaks in the morning. Uptake and degradation of POS initiates signaling cascades in the RPE. Upstream stimuli from various metabolic activities converge on mechanistic target of rapamycin complex 1 (mTORC1), and aberrant mTORC1 signaling is implicated in aging and age-related degeneration of the RPE. We measured mTORC1-mediated responses to RPE phagocytosis in vivo and in vitro. During the morning burst of POS shedding, there was transient activation of mTORC1-mediated signaling in the RPE. POS activated mTORC1 through lysosome-independent mechanisms, and engulfed POS served as a docking platform for mTORC1 assembly. The identification of POS as endogenous stimuli of mTORC1 in the RPE provides a mechanistic link underlying the photoreceptor-RPE interaction in the outer retina.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Humans
  • Lysosomes / metabolism*
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis*
  • Photoreceptor Cells / cytology
  • Photoreceptor Cells / metabolism
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism*
  • Signal Transduction


  • Mechanistic Target of Rapamycin Complex 1