Loss and recovery of neurofilament in the cat lateral geniculate nucleus following monocular retinal inactivation

Background: Postnatal development of the mammalian primary visual pathway occurs early in life and is guided by visually-driven afferent activity. Even a short duration of disrupted binocular vision can derail development of neural connections and produce a lasting monocular visual impairment, amblyopia. Temporary inactivation of the dominant retina with tetrodotoxin has emerged as a potential treatment for amblyopia that has exhibited superior potency compared to mainstay therapy in animal models. Notwithstanding its promise as a treatment for amblyopia, little is known about the impact of retinal inactivation on neurons within the primary visual pathway. Methods: We investigated the impact that monocular inactivation (MI) imposed at different postnatal ages has on neurofilament immunolabeling within eye-specific layers of the cat dorsal lateral geniculate nucleus (dLGN). Neurofilament is a constituent of the stable neuronal cytoskeleton and a sensitive marker for different kinds of visual deprivation that produce amblyopia. A comparison of the potential for neurofilament recovery was also examined after either MI or monocular deprivation (MD). Results: Data revealed a profound efficacy for MI to elicit reduction of neurofilament labeling in dLGN layers serving the inactivated eye. The effect of MI was greatest when administered early in development near the critical period peak, then declined considerably with age, though an effect was still observed at the oldest age examined. Despite the significant loss of neurofilament produced by MI, near complete recovery was measured when binocular vision was provided after the period of inactivation but this was not observed after MD. Conclusion: These results demonstrate the remarkable efficacy of MI to elicit significant modification of neurofilament within the dLGN throughout early postnatal development, and they also reveal a surprising capacity for recovery following the period of inactivation.