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Sophie Vanhunsel, Jolien Van houcke, Ilse Bollaerts, Lieve K M Moons; Fishing for neuroreparative strategies in the short-living Nothobranchius furzeri. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3113.
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© ARVO (1962-2015); The Authors (2016-present)
Today, a growing number of elderly is suffering from age-associated neuropathies. Intensive research efforts are therefore focused on stimulating neuroregeneration in the diseased central nervous system (CNS), a capacity that is unfortunately very limited in adult mammals and remains challenging to induce, especially in an aging environment. African turquoise killifish (N. furzeri) have a remarkable neurogenic and regenerative potential in their adult CNS. Moreover, by displaying aging characteristics similar to humans, this short-living teleost is ideally suited to investigate the underlying mechanisms that support successful regeneration in an aging environment.
Age-related changes in the killifish visual system were evaluated using (immuno)histochemistry ((I)HC), and techniques such as optical coherence tomography (OCT) and optokinetic response (OKR) test. Young, middle-aged, old and very old killifish were subjected to optic nerve crush (ONC), and axonal regeneration was investigated via biocytin tracing, IHC for synaptic repair and visual behavioral tests such as OKR and dorsal light reflex (DLR). Underlying cellular processes were analyzed via IHC.
Detailed analysis of the old killifish visual system revealed several senescence-associated manifestations, such as decreased visual acuity, retinal atrophy, reduced synaptic integrity in the retina, increased beta-galactosidase expression in both retina and brain, and declined neurogenesis in the ciliary marginal zone, a peripheral stem cell zone in the retina. When comparing optic nerve regeneration in young, middle-aged, old and very old killifish subjected to ONC, tectal reinnervation is delayed in aged fish. Strikingly, even though tectal reinnervation is eventually completed, they do not seem to functionally recover, indicative for a dysregulated synaptogenesis. Additional experiments are currently being performed to investigate the underlying mechanisms responsible for this impaired regenerative capacity in aged fish.
The obtained findings indicate the presence of several aging hallmarks in the aged killifish visual system, which seem to impact the regenerative capacities of these old fish. Our results urge further investigations into the underlying aging processes and pathways affecting the regenerative potential, thereby contributing to the search for effective neuroregenerative therapies in the aged mammalian CNS.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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