July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The role of NF-kB signaling in Müller glia-derived progenitor cell proliferation after NMDA damage
Author Affiliations & Notes
  • Isabella Palazzo
    The Ohio State University, Columbus, Ohio, United States
  • Kyle Deistler
    The Ohio State University, Columbus, Ohio, United States
  • Andrew J Fischer
    The Ohio State University, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Isabella Palazzo, None; Kyle Deistler, None; Andrew Fischer, None
  • Footnotes
    Support  NIH EY022030
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4610. doi:
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    • Get Citation

      Isabella Palazzo, Kyle Deistler, Andrew J Fischer; The role of NF-kB signaling in Müller glia-derived progenitor cell proliferation after NMDA damage. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4610.

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

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Purpose : Müller glia are the primary support cell of the retina and have the capacity to reprogram into proliferating Müller glia-derived progenitor cells (MGPCs). Müller glia-mediated regeneration in chick and mouse is limited, and in order to harness the regenerative potential of Müller glia we must further study the cell signaling pathways and mechanisms that govern MGPC proliferation and differentiaiton. NF-kB signaling is a mediator of immune response, and has also been shown to have roles in cell proliferation and cell survival. The purpose of this study is to study the role of NF-κB signaling in the avian and murine retina.

Methods : Postnatal 7-14 day chicks and p40 NF-κB-GFP reporter-mice were used for experiments. Microglia were ablated via intraocular injections of Clodronate liposomes (chick) or oral Plex4032 (mouse). Retinal damage was induced via intraocular injection of NMDA. NF-kB signaling was influenced by using pharmacological agents: Sulfasalazine, an inhibitor of NF-κB signaling, and Prostratin, an activator of NF-κB signaling. EdU was injected in all experimental paradigms to label proliferating cells. Retinal tissues were harvested and processed for immunofluorescence and photomicroscopy. Significance of difference in was determined using a 2-tailed T-test.

Results : We found that inhibition of NF-kB in NMDA damaged retinas significantly increased the number of proliferating MGPCs (ctrl-25.2±16.1 vs. sulfasalazine trt-81.4±32.0, n=5, p=0.0217), while activation of NF-kB resulted in decreased MGPC proliferation (ctrl-101.3±29.3 vs. prostratin trt-49±11.9, n=6, p=0.002). In the absence of microglia, inhibition of NF-kB signaling in damaged retinas did not alter MGPC proliferation (ctrl-23±38.1 vs. sulfasalazine trt-23±21.5, n=7, p=0.957), while activation of NF-kB signaling resulted in a significant increase in MGPC proliferation (ctrl-18±10.5 vs. prostratin trt-54±33, n=8, p=0.002). In the damaged mouse retinas, the NF-kB-GFP reporter was observed in Müller glia, however this reporter was greatly reduced in Müller glia when the microglia were ablated.

Conclusions : These results show that NF-kB signaling plays an important role in regulating MGPC proliferation in the chick retina. Further, NF- kB is part of an important network of signaling between microglia and Müller glia that affects formation of MGPCs. Thus, NF-kB is a promising target to guide MGPC-mediated retinal regeneration.

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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