June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Retinoic acid signaling promotes proliferation and neuronal differentiation from Muller glia-derived progenitor cells in the avian retina.
Author Affiliations & Notes
  • Levi Todd
    Neuroscience, Ohio State University, Columbus, Ohio, United States
  • Lilianna Suarez
    Neuroscience, Ohio State University, Columbus, Ohio, United States
  • Colin Quinn
    Neuroscience, Ohio State University, Columbus, Ohio, United States
  • Andrew J Fischer
    Neuroscience, Ohio State University, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Levi Todd, None; Lilianna Suarez, None; Colin Quinn, None; Andrew Fischer, None
  • Footnotes
    Support  NIH-EY022030–4
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 802. doi:
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    • Get Citation

      Levi Todd, Lilianna Suarez, Colin Quinn, Andrew J Fischer; Retinoic acid signaling promotes proliferation and neuronal differentiation from Muller glia-derived progenitor cells in the avian retina.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):802.

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

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Abstract

Purpose : Understanding the signaling pathways that regulate the transition of Muller glia into neurogenic Muller glia-derived progenitor cells (MGPCs) is imperative to promoting retinal regeneration. This study investigates how Retinoic acid (RA) signaling impacts the proliferative and neurogenic potential of MGPCs in the chick retina in vivo.

Methods : Experiments were performed on posthatch chicks (7-21 days old). Compounds were delivered via intraocular injections. An analog of retinoic acid (TTNPB) and a RA-receptor inhibitor (BMS 493) were used to modulate RA-signaling. Retinas were damaged by an injection of N-Methyl-D-aspartate (NMDA). FGF2 was used to stimulate MGPC formation in undamaged retinas. EdU was applied to label proliferating cells. Following experimental paradigms, retinas were processed for immunoflourescence and digital photomicroscopy. Significance of difference was determined using a paired, two-tailed t-test.

Results : We found that stimulating RA-signaling in NMDA damaged retinas significantly increased Muller glia proliferation (control 16±5.5 vs. TTNPB treated 52±7.4, n=5, p<0.01). Conversely, inhibition of the RA-receptor decreased Muller glia proliferation in damaged retinas (control 87±55.9 vs. BMS 493 treated - 20±13.7, n=6, p<.05). We found that Pax6 expression was increased in Muller glia by RA-signaling and decreased by inhibition of the RA-receptor. FGF2 is the only known factor that can stimulate MGPC formation in the uninjured chick retina. We found that TTNPB combined with FGF2 increased MGPC proliferation (FGF2 14.4±6.3 vs. FGF2+TTNPB-33.2±6.8, n=5, p<.01). Furthermore, RA-signaling promoted the expression of cFOS and Pax6 in Muller glia in FGF2 treated retinas. Inhibition of RA-receptor in FGF2-treated retinas suppressed the proliferation of MGPCs (FGF2 68.5±22.6 vs. FGF2+BMS493 27.4±19.9, n=7,p<.003). Lastly, we found that stimulating RA-signaling in damaged retinas significantly increased neurogenesis from MGPCs (+37.9%±25.9, n=5, p=0.01).

Conclusions : Our data indicate that RA-signaling plays a significant role in promoting the proliferation and neurogenic capacity of MGPCs. Furthermore, we find that RA-signaling coordinates with MAPK-signaling to stimulate MGPC-formation in the absence of damage. This work provides novel data suggesting that RA-signaling is a promising target to promote retinal regeneration.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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