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Diana Mitchell, Deborah L Stenkamp; Characterization of Microglia During Retinal Regeneration in Zebrafish. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2239.
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© ARVO (1962-2015); The Authors (2016-present)
Zebrafish, in contrast to mammals, are able to regenerate dead or damaged retinal neurons. It remains to be determined if microglia, resident macrophages of both fish and mammalian retina, play a significant role in retinal regeneration. Since macrophages are essential to coordinating the transition from inflammation to tissue repair, understanding their function in retinal regeneration could lead to strategies that aim to support retinal regeneration in humans. Microglia have recently been shown to play a role in shaping neuronal synapses during development, suggesting that they could participate in a similar fashion during regeneration. Such findings would contribute to NEI’s Audacious Goal “to regenerate neurons and neural connections in the eye and visual system.” Here we examine characteristics of microglia over the course of retinal regeneration.
Selective lesioning of zebrafish retinas was performed by intravitreal injection of the neurotoxin ouabain. Control retinas were injected with saline solution. At multiple time points post-injury, regenerating and control retinas were sectioned and stained for markers of microglia, Müller glia, and retinal neurons, then examined by confocal microscopy. In some experiments, a transgenic line was used to visualize microglia. Images were analyzed for circularity of microglia and retinal location.
Three days post-injury, microglia displayed non-ramified and circular morphology, indicative of activation, while microglia in control retinas remained ramified (p=4.3x10-9). Microglia in regenerating retina retained this morphology during timeframes which, in parallel studies, appeared to include neuronal synapse remodeling (p=.001). Further, microglia localized to the inner and outer plexiform layers, regions of the retina where neuronal synapses are reestablished.
Morphology and localization of microglia suggest that microglia may actively participate in shaping neuronal synapses during regeneration. Current experiments are probing the effects of immune modulation during retinal regeneration to determine if altering microglial activation has an effect on regenerative outcome.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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