ABSTRACT
Interleukin-6 (IL-6) is involved in different processes of the central nervous system. Our aims were to investigate the effect of IL-6 on retinotectal topography and on different signaling pathways. Rats were submitted to an intravitreous injection of either IL-6 (50 ng/ml) or PBS (vehicle) at postnatal day 10 (PND10). At PND11 or PND14, different groups were processed for western blot, histochemistry or immunofluorescence analysis. IL-6 treatment leads to an increase in pSTAT-3 levels in the retina and a disruption in the retinotectal topographic map, suggesting that a transient increase in interleukin-6 levels may impact neural circuitry development.
Subject(s)
Interleukin-6/pharmacology , Visual Pathways/growth & development , Animals , Interleukin-6/administration & dosage , Interleukin-6/physiology , Intravitreal Injections , Phosphorylation , Rats , Retina/drug effects , Retina/growth & development , Retina/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , Superior Colliculi/drug effects , Superior Colliculi/growth & development , Superior Colliculi/physiology , Visual Pathways/drug effects , Visual Pathways/physiologyABSTRACT
OBJECTIVE: Interleukin 4 (IL-4) is an anti-inflammatory cytokine related to different aspects of central nervous system development such as survival, proliferation, and differentiation, among others. Our goals were to investigate the effect of intravitreous treatment with IL-4 on the activation of downstream signaling pathways in the retina and the distribution of retinal axons within the superior colliculus (SC). MATERIAL AND METHODS: Lister hooded rats were submitted to an intravitreous injection of either IL-4 (5 U/µL) or PBS (vehicle) at postnatal day 10 (PND10). At PND11 or PND14, retinas were processed for Western blot or immunohistochemistry. At PND13, a group of animals received an intraocular injection of an anterograde tracer in the left (untreated) eye in order to label the uncrossed retinotectal axons. RESULTS: Our data revealed that intravitreous treatment with IL-4 at PND10 leads to a decrease in GFAP content and a sustained increase in the phosphorylation of STAT6 and ERK levels in the retina. IL-4 also increases retinal axonal arbors within the SC, compared to control groups. CONCLUSIONS: These data suggest that a single in vivo treatment with IL-4 during the early stages of development modulates signaling pathways in the retina, resulting in altered binocular subcortical visual connectivity.
