Retinal microglia signaling affects Müller cell behavior in the zebrafish following laser injury induction.

Conedera, Federica Maria; Quintela Pousa, Ana Maria; Mercader Huber, Nadia Isabel; Tschopp, Markus; Enzmann, Volker (2019). Retinal microglia signaling affects Müller cell behavior in the zebrafish following laser injury induction. GLIA, 67(6), pp. 1150-1166. Wiley-Blackwell 10.1002/glia.23601

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Microglia are the resident tissue macrophages of the central nervous system including 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 bidirectional 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 the absence of immune cells after injury have not been investigated in detail in adult zebrafish. Here, we develop a model of focal retinal injury combined with pharmacological treatments for immune cell depletion in zebrafish. The retinal injury was induced by a diode laser to damage photoreceptors. Two pharmacological treatments were used to deplete either macrophage-microglia (PLX3397) or selectively eliminate peripheral macrophages (clodronate liposomes). We show that PLX3397 treatment hinders 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. In the untreated fish, Müller cells react after injury induction showing glial fibrillary acidic protein (GFAP), Phospho-p44/42 MAPK (Erk1/2), and PCNA upregulation. However, in the immunosuppressed animals, GFAP and phospho-p44/42 MAPK (Erk1/2) expression was not upregulated overtime and the reentry in the cell cycle was not affected. Thus, microglia and Müller cell signaling is pivotal to unlock the regenerative potential of Müller cells in order to repair the damaged retina.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde

UniBE Contributor:

Conedera, Federica Maria; Quintela Pousa, Ana Maria; Mercader Huber, Nadia Isabel; Tschopp, Markus and Enzmann, Volker

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0894-1491

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Volker Enzmann

Date Deposited:

19 Jul 2019 09:14

Last Modified:

23 Oct 2019 06:18

Publisher DOI:

10.1002/glia.23601

PubMed ID:

30794326

Uncontrolled Keywords:

Müller cells degeneration laser treatment macrophages microglia regeneration retina zebrafish

BORIS DOI:

10.7892/boris.131149

URI:

https://boris.unibe.ch/id/eprint/131149

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