Resumo

OBJECTIVE: The development of retinotectal topography involves an early event that is mediated by attractive/ repulsive cues followed by an activity-driven synaptic refinement which occur within the first two postnatal week. Cytokines are neuroregulatory factors synthesized by glial and neuronal cells which participate on CNS development and pathogenesis. Many reports suggest that interleukin-2 (IL-2), a pro-inflammatory cytokine, act on neural plasticity and synaptic activity modulation. Therefore, the aim of this work was study the in vivo IL-2 effect upon glial activation in retina and superior colliculi and the distribution of uncrossed retinotectal connections. METHODS: Lister Hooded rats were submitted to IL-2 or PBS injections in the right eye at PND10 (1X 156 U/ 0,5 μL) or at PND7/10/13 (3 X 50U/μL). At PND13, both groups received a HRP injection in left eye to tracer the uncrossed retinotectal projections. Additionally, at PND14, retinas and superior colliculi were processed by immunohistochemistry or western blot for GFAP. The retinal cells types were visualized by Nissl staining and retinal inflammation analyzed by CD11b immunohistochemistry. RESULTS: Our results show that multiple intraocular injections of PBS or IL-2 lead to an increase in retinal GFAP immunoreactivity in parallel to an inflammatory profile. Furthermore, both treatments trigger slightly sprouting in the retinotectal axons within superior colliculus compared to untreated animals. Alternatively, single IL-2 intravitreous injection enhances retinal GFAP immunolabeling compared to single PBS injection, without inducing inflammation. Moreover, IL-2 acute treatment induces a robust rupture in the uncrossed retinotectal projection of the intact eye compared to PBS-treated or untreatead rat. Superior colliculi GFAP content remained unchanged after all conditions. CONCLUSIONS: Our data suggest that exogenous interleukin-2 or multiple injections-derived inflammation in retina could modulate glial activation and probably retinal ganglion cells activity, which in turn alters the distribution of terminal axons on the superior colliculus.