July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Mouse embryonic stem cell-derived extracellular vesicles reactivate in vivo Müller progenitor cells of NMDA-damaged retinas rescuing retinal function
Author Affiliations & Notes
  • Alejandra Young
    Ophthalmology, Stein Eye Institute, Los Angeles, California, United States
  • Diana Katsman
    Ophthalmology, Loma Linda University, Loma Linda, California, United States
  • Debora B Farber
    Ophthalmology, Stein Eye Institute, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Alejandra Young, None; Diana Katsman, None; Debora Farber, None
  • Footnotes
    Support  Vision of Children Grant #20142326
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3122. doi:
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      Alejandra Young, Diana Katsman, Debora B Farber; Mouse embryonic stem cell-derived extracellular vesicles reactivate in vivo Müller progenitor cells of NMDA-damaged retinas rescuing retinal function. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3122.

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

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Abstract

Purpose : Based on our previous in vitro studies demonstrating that mouse embryonic stem cell (ESC)-derived extracellular vesicles (mESEVs) induce cultured human Müller glia to dedifferentiate, turn on an early retinogenic program, and differentiate towards cells of amacrine, ganglion cell, and rod photoreceptor lineage, we have now investigated the ability of mESEVs to reactivate Müller cells in vivo, using an NMDA-injury mouse model of retinal disease.

Methods : ESEVs were isolated from the culture medium of mouse ESCs by ultracentrifugation. Baseline retinal function was obtained measuring the ERGs from each eye of several mice cohorts (7 animals each) prior to and 24 hours after NMDA damage of both eyes. 48 hours later, left eyes were injected intraocularly or sub-retinally with different doses of mESEV suspension while the right eyes were similarly injected with 0.1 M PBS. All injections contained BrdU to assess cell proliferation. Retinal function was examined 15, 30 and 60 days post-ESEV injection and the % of functional recovery was calculated from the peak amplitudes of the ERG b-waves in mESEV-treated and untreated eyes. mESEV-injected retinas were imaged and compared to NMDA-damaged and untreated retinas to see morphological changes. In addition, the eyes of a subset of animals from each experimental group were analyzed by confocal microscopy.

Results : ERGs of several mESEV-treated retinas showed a remarkable improvement when compared to those of control NMDA-injured, PBS-injected retinas. Moreover, confocal microscopy allowed us to identify proliferating cells in mESEV-treated retinas; many of these cells co-localized with Cralbp (marker for Müller cells) and few others with Gad67 and Syntaxin1a (markers for amacrine cells).

Conclusions : mESEV-treatment led to retinal function improvement in mice with NMDA-damaged retinas probably due to proliferation, dedifferentiation and trans-differentiation of Müller cell progenitors into retinal neurons.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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