July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Retinal microglia signaling affects Muller cell behavior in the zebrafish following laser injury induction
Author Affiliations & Notes
  • Federica Maria Conedera
    Experimental Ophthalmology, Inselspital-University of Bern, Bern, Switzerland
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    Commercial Relationships   Federica Conedera, Inselspital-University of Bern (E)
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Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3993. doi:
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      Federica Maria Conedera; Retinal microglia signaling affects Muller cell behavior in the zebrafish following laser injury induction. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3993.

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

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Abstract

Purpose : Microglia are the resident tissue macrophages of the retina. Under pathophysiological conditions, microglia can signal to Müller cells, the major glial component of the retina, affecting their morphological, molecular, and functional responses. Microglia-Müller cell interactions appear to be bi-directional shaping the overall injury response in the retina. Hence, microglia and Müller cell responses to disease and injury have been ascribed both positive and negative outcomes. However, Müller cell reactivity and survival in absence of immune cells after injury have not been investigated in detail in adult zebrafish.

Methods : A model of focal retinal injury combined with pharmacological treatments for immune cell depletion in zebrafish was employed. The retinal injury was induced by a 532 nm diode laser to damage photoreceptors. Two pharmacological treatments were used to deplete either macrophage-microglia (PLX3397) or selectively eliminate peripheral macrophages (clodronate-liposomes). Retinal degeneration and regeneration was examined at different time points post injury induction by in vivo imaging (OCT) and morphological analysis (H&E staining). Furthermore, immunohistochemical analyses (e.g., GS, GFAP, and PCNA) were used to characterize how microglia affect Müller cell response to the laser injury.

Results : PLX3397 treatment induced immune cell depletion hindering retinal regeneration in zebrafish, which is reversed by microglial repopulation. On the other hand, selective macrophage elimination did not affect the kinetics of retinal regeneration. The absence of retinal microglia and macrophages leads to dysregulated Müller cell behavior. Unlike the untreated fish, where Müller cells were activated after injury induction, immunosuppressed animals showed no activation. However, the re-entry in the cell cycle was not affected in the PLX3397 treated fish.

Conclusions : Without microglia signaling Müller cells can still dislocate into the damage area despite not being activated. This dysregulated Müller cell behavior results in impaired regeneration in the retina of immunosuppressed fish. Thus, microglia and Müller cell signaling is pivotal to unlock the regenerative potential of Müller cells in order to repair the damaged retina.

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

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