PUBLICATION

TNFα Induces Müller Glia to Transition From Non-proliferative Gliosis to a Regenerative Response in Mutant Zebrafish Presenting Chronic Photoreceptor Degeneration

Authors: Iribarne, M., Hyde, D.R., Masai, I.
ID: ZDB-PUB-200131-6
Date: 2019
Source: Frontiers in cell and developmental biology 7: 296 (Journal)
Registered Authors: Hyde, David R., Iribarne, Maria, Masai, Ichiro
Keywords: Aipl1, Müller glia, genetic mutant, photoreceptor degeneration, regeneration, rod precursors, zebrafish
MeSH Terms: none
PubMed: 31998714 Full text @ Front Cell Dev Biol

Abstract

Unlike mammals, zebrafish have the capacity to regenerate neurons in response to damage. Most zebrafish retinal injury models employ acute damage, which is unlike the chronic, gradual damage that occurs in human retinal diseases. Here, we studied the regenerative response in the zebrafish aipl1b mutant, gold rush (gosh). In gosh mutants, both cones and rods degenerate by 3 weeks post-fertilization (wpf). Müller glia do not exhibit a regenerative response by 3 wpf; however, they do present non-proliferative gliosis. Only at 5 wpf, is proliferation of Müller cells and rod precursor cells activated. Rods start to recover at 5 wpf and by 12 wpf they reach a level of recovery comparable to wild type, but cones remain absent in the adult stage. TNFα was detected in degenerating cones at 5-7 wpf and in Müller glia at 7 wpf in gosh mutants. At 5 wpf, proliferating Müller glia express Sox2, followed by Pax6 expression in neuronal progenitor cells (NPCs), confirming that the neuronal regeneration program is activated in gosh mutants after 5 wpf. Although acute light-induced damage did not activate proliferation of Müller glia, TNFα injection caused Müller glia to commence a proliferative response at 3 wpf in gosh mutants. These results suggest that Müller glia transition from non-proliferative gliosis to a regenerative state in gosh mutants, and that ectopic introduction of TNFα promotes this Müller cell transition even at 3 wpf. Thus, zebrafish gosh mutants provide a useful model to investigate mechanisms underlying retinal regeneration in a chronic photoreceptor degeneration model.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	aipl2^s341/s341; nt11Tg	standard conditions	Days 21-29	Muller cell cell body	IHC	Fig. 3
EGFP	aipl2^s341/s341; nt11Tg	standard conditions	Days 21-29	Muller cell cell projection	IHC	Fig. 3
EGFP	aipl2^s341/s341; nt19Tg	standard conditions	Days 30-44	retinal rod cell	IHC	Fig. S2
EGFP	aipl2^s341/s341; nt19Tg	standard conditions	Days 21-29	retinal rod cell	IHC	Fig. S2
EGFP	nt11Tg	standard conditions	Days 21-29	Muller cell cell body	IHC	Fig. 3
EGFP	nt11Tg	standard conditions	Days 21-29	Muller cell cell projection	IHC	Fig. 3
EGFP	nt19Tg	standard conditions	Days 21-29	retinal rod cell	IHC	Fig. S2
EGFP	nt19Tg	standard conditions	Days 30-44	retinal rod cell	IHC	Fig. S2
gfap	aipl2^s341/s341	standard conditions	Days 30-44	eye	RTPCR	Fig. 3
gfap	aipl2^s341/s341	standard conditions	Days 21-29	head	RTPCR	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
aipl2^s341/s341	standard conditions	Days 21-29	head gfap expression increased amount, abnormal	Fig. 3
aipl2^s341/s341	standard conditions	Days 30-44	eye gfap expression increased amount, abnormal	Fig. 3
aipl2^s341/s341	standard conditions	Days 30-44	eye tnfa expression increased amount, abnormal	Fig. 4
aipl2^s341/s341	standard conditions	Days 45-89	eye tnfa expression increased amount, abnormal	Fig. 4
aipl2^s341/s341; nt11Tg	standard conditions	Days 21-29	Muller cell ab2-pcna labeling decreased amount, abnormal	Fig. 3
aipl2^s341/s341; nt11Tg	standard conditions	Days 21-29	Muller cell cell projection EGFP expression increased amount, abnormal	Fig. 3
aipl2^s341/s341; nt11Tg	standard conditions	Days 21-29	Muller cell hypertrophic, abnormal	Fig. 3
aipl2^s341/s341; nt11Tg	standard conditions	Days 21-29	Muller cell reactive gliosis increased process quality, abnormal	Fig. 3
aipl2^s341/s341; nt11Tg	standard conditions	Days 21-29	retinal outer nuclear layer ab2-pcna labeling decreased amount, abnormal	Fig. 3
aipl2^s341/s341; nt19Tg	standard conditions	Days 21-29	retinal rod cell decreased amount, abnormal	Fig. S2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
nt11Tg	Tg(gfap:EGFP)	Transgenic Insertion
nt19Tg	Tg(rho:Eco.NfsB-EGFP)	Transgenic Insertion
oki061Tg	Tg(gnat2:GFP)	Transgenic Insertion
s341		Point Mutation	aipl2

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
aipl2^s341/s341
aipl2^s341/s341; nt11Tg
aipl2^s341/s341; nt19Tg
aipl2^s341/s341; oki061Tg
nt11Tg
nt19Tg
oki061Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Iribarne et al., 2019 ZDB-PUB-200131-6 PMID:31998714

TNFα Induces Müller Glia to Transition From Non-proliferative Gliosis to a Regenerative Response in Mutant Zebrafish Presenting Chronic Photoreceptor Degeneration

Iribarne et al., 2019

ZDB-PUB-200131-6
PMID:31998714