July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
mTOR Signaling and Human Retinal Ganglion Cell Development and Function
Author Affiliations & Notes
  • Pooja Teotia
    Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Matthew J Van Hook
    Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Iqbal Ahmad
    Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Footnotes
    Commercial Relationships   Pooja Teotia, None; Matthew Van Hook, None; Iqbal Ahmad, None
  • Footnotes
    Support  National Eye Institute/National Health Institute
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 653. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Pooja Teotia, Matthew J Van Hook, Iqbal Ahmad; mTOR Signaling and Human Retinal Ganglion Cell Development and Function. Invest. Ophthalmol. Vis. Sci. 2019;60(9):653.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : The degeneration of retinal ganglion cells (RGCs) is the unifying theme in glaucoma, a complex group of disorders. However, their susceptibility to degeneration in the heterogeneous disease remains poorly understood. It is likely that it may be acquired during development, which is unmasked with the progression of the disease in adults. To test this premise we are characterizing mechanism(s) underlying human RGC development in induced pluripotent stem cells (iPSCs) models. Here, we demonstrate that the mTOR signaling pathway plays a significant role in the differentiation and function of human RGCs.

Methods : Human iPSCs were differentiated along the RGC lineage using our chemically defined protocol, where mTOR signaling was activated by lentivirus-mediated transduction of Tsc-2 (tuberous sclerosis complex 2) or repressed by exposure of cells to rapamycin. The effect of perturbed signaling was then studied with respect to RGC differentiation, function, and neuritogenesis.

Results : Western blot analysis of the levels of pS6 in human RGCs after Tsc-2 shRNA lentivirus transduction and rapamycin treatment confirmed the activation and repression of mTOR signaling. Q-PCR and immunocytochemical analyses of human RGCs upon mTOR activation revealed a significant increase in the expression of RGC-specific markers and axon guidance molecules, compared to controls. Electrophysiological recordings demonstrated that the activated mTOR pathway contributed to the frequent and regular spontaneous action potentials, and overall network excitability in human RGCs that appeared to be reduced in controls. Additionally, sholl analysis of human RGCs in response to activation in mTOR signaling showed increased neurite complexities, versus controls.

Conclusions : Our results posit the mTOR signaling as a significant regulator of human RGC differentiation, function, and neuritogenesis and as such may help in understanding glaucomatous degeneration and formulating regenerative strategies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×