Inhibition of the TGFβ Pathway Enhances Retinal Regeneration in Adult Zebrafish.

Tappeiner, Christoph; Maurer, Ellinor; Sallin, Pauline; Bise, Thomas; Enzmann, Volker; Tschopp, Markus (2016). Inhibition of the TGFβ Pathway Enhances Retinal Regeneration in Adult Zebrafish. PLoS ONE, 11(11), e0167073. Public Library of Science 10.1371/journal.pone.0167073

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In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish. Immunohistochemical staining for phosphorylated Smad3 was elevated during retinal regeneration, and phosphorylated Smad3 co-localized with proliferating cell nuclear antigen and glutamine synthetase, indicating TGFβ pathway activation in proliferating Müller glia. Inhibiting the TGFβ signaling pathway using a small molecule inhibitor (SB431542) resulted in accelerated recovery from retinal degeneration. Accordingly, we observed increased cell proliferation in the outer nuclear layer at days 3 to 8 after MNU treatment. In contrast to the observations in the heart and the fin, the inhibition of the TGFβ signaling pathway resulted in increased proliferation after the induction of retinal degeneration. A better understanding of the underlying pathways with the possibility to boost retinal regeneration in adult zebrafish may potentially help to stimulate such proliferation also in other species.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Tappeiner, Christoph

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Christoph Tappeiner

Date Deposited:

26 Jan 2017 15:47

Last Modified:

29 Jan 2017 06:09

Publisher DOI:

10.1371/journal.pone.0167073

PubMed ID:

27880821

BORIS DOI:

10.7892/boris.93122

URI:

https://boris.unibe.ch/id/eprint/93122

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