July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
TrkB-signaling potentiates Müller glia proliferation in damaged and FGF2-treated retinas.
Author Affiliations & Notes
  • Levi Todd
    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; Colin Quinn, None; Andrew Fischer, None
  • Footnotes
    Support  EY022030-5
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4596. doi:
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      Levi Todd, Colin Quinn, Andrew J Fischer; TrkB-signaling potentiates Müller glia proliferation in damaged and FGF2-treated retinas.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4596.

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

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Purpose : Müller glia are the primary support cells in the vertebrate retina. In response to injury, Müller glia can reprogram into proliferating neurogenic progenitor cells that can replace neurons. The ability of Müller glia to regenerate neurons is diminished in higher vertebrates. Identification of signaling pathways that enhance the reprograming capacity of Müller glia is expected to guide therapeutic strategies for cell replacement. This study investigates how TrkB-signaling impacts the ability of Müller glia to transition into proliferating Müller glia-derived progenitor cells (MGPCs) in the chick retina in vivo.

Methods : Posthatch chicks (7 days old) were used for experiments. Compounds were applied via intraocular injections. In each experiment one eye served at the “compound” treated eye and the contralateral eye served as the “vehicle” treated control. To activate TrkB-signaling we used LM22A-4 (Sigma) an agonist to TrkB. To inhibit TrkB-signaling we used the TrkB-antagonist ANA 12 (Tocris). Intraocular injections of N-Methyl-D-aspartate (NMDA) was used to elicit neuronal cell death. FGF2 was used to stimulate Müller glia proliferation in undamaged retinas. EdU was applied to label proliferating cells. The TUNEL assay was utilized to measure cell death. Following experiments, retinas were harvested for immunoflourescence and digital photomicroscopy. Two-tailed t-tests determined the significance of difference.

Results : The activation of TrkB-signaling with LM22A-4 significantly increased MGPC proliferation in NMDA damaged retinas (control –29.5 vs. LM22A-4 treated –74.2, n=7, p<.01). This effect occurred independent of cell death (control - 14±13.8 vs. LM22A-4 treated –10.8±10, n=4, p=0.7), elevated microglial reactivity (CD45-levels) and microglia proliferation (control –8±6.4 vs. LM22A-4 treated –3±1.8, n=4, p=0.1). Activation of TrkB-signaling in combination with FGF2 significantly increased the MGPC prolieration in the absence of damage (FGF2 treated –20±18 vs. FGF2+LM22A-4 treated -45±14, n=8, p<.01). The TrkB-antagonist, ANA 12, significantly inhibited the formation of proliferating MGPCs in damaged retinas (control –117.7±17 vs. ANA 12 treated -89.1±23.5, n=10, p<0.01) and this effect was independent of cell survival (control –18.6±3.8vs. ANA 12 treated –38.6±19, n=3, p<.01).

Conclusions : Our data suggests that TrkB-signaling potentiates MGPC formation in damaged and FGF2-treated retinas.

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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