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Characterization of proliferative, glial and angiogenic responses after a CoCl 2 ‐induced injury of photoreceptor cells in the adult zebrafish retina
Author(s) -
Medrano Matias Pedro,
Pisera Fuster Antonella,
Sanchis Pablo Antonio,
Paez Natalia,
Bernabeu Ramon Oscar,
Faillace Maria Paula
Publication year - 2018
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14113
Subject(s) - retina , muller glia , zebrafish , regeneration (biology) , vascular endothelial growth factor , retinal regeneration , microbiology and biotechnology , chemistry , ionotropic effect , progenitor cell , biology , glutamate receptor , receptor , cancer research , neuroscience , stem cell , biochemistry , vegf receptors , gene
The adult zebrafish is considered a useful model for studying mechanisms involved in tissue growth and regeneration. We have characterized cytotoxic damage to the retina of adult zebrafish caused by the injection of cobalt chloride (CoCl 2 ) into the vitreous cavity. The CoCl 2 concentration we used primarily caused injury to photoreceptors. We observed the complete disappearance of cones, followed by rods, across the retina surface from 28 to 96 hr after CoCl 2 injury. The loss of 30% of bipolar cells was also observed by 50 hr after lesion (hpl). CoCl 2 injury provoked a strong induction of the proliferative activity of multipotent Müller glia and derived progenitors. The effect of CoCl 2 on retina cells was significantly reduced by treatment with glutamate ionotropic receptor antagonists. Cone photoreceptor regeneration occurred 25 days after injury. Moreover, a single dose of CoCl 2 induced vascular damage and regeneration, whereas three injections of CoCl 2 administered weekly provoked neovascular‐like changes 20 days after injury. CoCl 2 injury also caused microglial reactivity in the optic disc, retina periphery and fibre layer. CoCl 2 ‐induced damage enhanced pluripotency and proneural transcription factor gene expression in the mature retina 72 hpl. Tumour necrosis factor alpha, vascular endothelial growth factor ( VEGF ) and VEGF receptor mRNA levels were also significantly enhanced by 72 hpl. The injury paradigm we have described in this work may be useful for the discovery of signalling molecules and pathways that participate in the regenerative response and it may serve as a model to screen for compounds that could potentially treat aberrant angiogenesis.