Purchase this article with an account.
Lieve K M Moons, Jessie Van houcke, Kim Lemmens, Ilse Bollaerts, Lies De Groef, Inge Van Hove; The effect of aging on neuroregenerative capacities: insights from the senescent zebrafish retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4965.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
As adult mammals lack the capacity to regenerate lost or damaged neurons, age-related deterioration of the central nervous system (CNS) seriously constrains life quality of a growing number of elderly. Despite intensive research, induction of neuronal and axonal regeneration and subsequent functional recovery of the diseased mammalian CNS remains a challenge, especially in an aging environment. In contrast to mammals, adult zebrafish have a high neurogenic and regenerative capacity. As they were recently identified to age gradually, they form an ideal model to study the effects of aging on regeneration potential. We focus on the zebrafish retinotectal system, a powerful system to study neurogenesis, neuronal survival and axonal regrowth after damage.
The overall effects of aging on retinal and optic nerve morphology in zebrafish were evaluated using immunohistological methods (IHC) for detection of neurogenesis, apoptosis, synaptic integrity and inflammation. Aged zebrafish were subjected to optic nerve crush (ONC) and axonal regeneration was followed using biocytin tracing and GAP43 immunostainings within the retinotectal system. Underlying processes were analysed via IHC and Western blotting.
Detailed morphometric and immunohistochemical analyses of the aged zebrafish eye confirmed the occurrence of age-related retinal atrophy and revealed a clear manifestation of ‘inflammaging’ in the retina and optic nerve. These hallmarks of aging are accompanied by a reduction in the endogenous neurogenic capacity of the ciliary marginal zone and by a diminished tectal innervation. Importantly, we observed a significant delay in axonal regeneration after optic nerve crush, resulting in a diminished reinnervation of the tectum in 2- year-old zebrafish. The mechanisms underlying this decreased regenerative potential are currently being investigated.
Our results indicate the presence of several hallmarks of aging in the aged zebrafish retinotectal system, which seem to influence regeneration capacities. Therefore, the zebrafish optic system offers a valuable subject to study the effects of aging on neuroprotection and axonal regeneration and to elucidate underlying mechanisms and pathways. These studies might unveil new targets for the development of novel regenerative strategies in the senescent mammalian CNS.
This PDF is available to Subscribers Only