MICROGLIAL ACTIVATION IN THE CAT DORSAL LATERAL GENICULATE NUCLEUS FOLLOWING RETINAL INACTIVATION

Abstract

Amblyopia is the leading cause of monocular vision loss in children. Success in treating amblyopia using conventional methods such as patching and atropine penalization are hindered by compliance issues, rigid treatment schedules, and a short treatment window during young childhood. Thus, alternative treatments addressing these barriers are necessary to improve visual outcomes. Retinal silencing, by administering intravitreal injections of tetrodotoxin (TTX), is a potential treatment for amblyopia in lieu of patching or penalization. Fellow eye retinal silencing has shown good results in promoting visual recovery of the deprived eye, with no permanent detriment to the silenced eye. However, the underlying mechanisms that protect the eye during silencing are not fully understood. Microglia are a subtype of glial cells involved in mediating the development of the synaptic network in the central nervous system. The current study sought to determine if microglia are involved in a homeostatic response that protects the synaptic network against lowered neural activity elicited by retinal silencing. In other words, how are synapses-serving the inactivated eye protected from perturbation? Microglial activation was investigated as a possible protective mechanism by measuring ionized calcium binding adaptor molecule 1 (Iba1) immunolabeling within the silenced- eye layers of the dorsal lateral geniculate nucleus. The results of this study revealed that retinal silencing in young animals activates microglia, and that retinal silencing in older animals did not elicit such activation. These findings raise the possibility that activation of microglia mediates a homeostatic response to protect against retinal silencing-induced synaptic modifications. The current study also showed that retinal silencing in younger animals activates microglial transiently, as activation is not sustained following TTX with a period of binocular vision. As TTX treatment stands as a possible alternative treatment for human amblyopia, it is important to understand how TTX affects the synaptic network of the visual system.