Intravitreous interleukin-2 treatment and inflammation modulates glial cells activation and uncrossed retinotectal development

Espírito-Santo, Sheila; Mendonça, Henrique Rocha; Menezes, Grasielle Duarte; Goulart, Vanessa Gama; Tavares-Gomes, Ana Lúcia; Marra, Camila; Melibeu, A.C.F.; Serfaty, Claudio Alberto; Sholl‐Franco, Alfred; Campello-Costa, Paula

doi:10.1016/j.neuroscience.2011.10.034

Cited by 11 publications

(10 citation statements)

References 77 publications

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“…Several studies have demonstrated multiple effects of cytokines upon the visual system [25,28,29]. Here, we investigated whether in vivo IL-6 treatment modulates the distribution of retinotectal axons during the development of visual circuits.…”

Section: Resultsmentioning

confidence: 99%

“…The data showed that chronic treatment with either IL-2 or vehicle induces inflammation and plasticity in the uncrossed retinotectal axons. On the other hand, acute IL-2 intravitreous injection at an early stage of development leads to a rearrangement of the intact, nontreated eye without producing any intraretinal inflammation [25]. Therefore, in order to analyze the effect of IL-6 upon the retinotectal pathway, we decided to use a single intravitreous injection to avoid the presence of inflammation, which is recognized as an important element to induce plasticity [34,38].…”

Section: Discussionmentioning

confidence: 99%

“…Previously, our group demonstrated that different mechanisms are involved in the retinotectal development and plasticity [21,22,23,24]. Recently, we have shown that IL-2 intravitreous treatment during the critical period results in a sprouting of uncrossed retinotectal axons [25] . The aim of the present study was to evaluate the effect of a single intravitreous injection of IL-6 at different stages of development upon the distribution of retinal axons within the SC, which reveals the specificity of sensory circuits.…”

Section: Introductionmentioning

confidence: 99%

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Intravitreous Injection of Interleukin-6 Leads to a Sprouting in the Retinotectal Pathway at Different Stages of Development

Menezes

Goulart

Espírito-Santo³

et al. 2016

Neuroimmunomodulation

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Objective: The development of retinotectal pathways form precise topographical maps is usually completed by the third postnatal week. Cytokines participate in the development and plasticity of the nervous system. We have previously shown that in vivo treatment with interleukin 2 disrupts the retinocollicular topographical order in early stages of development. Therefore, we decided to study the effect of a single intravitreous injection of IL-6 upon retinotectal circuitry in neonates and juvenile rats. Materials and Methods: Lister Hooded rats received an intravitreous injection of IL-6 (50 ng/ml) or vehicle (PBS) at either postnatal day (PND)10 or PND30 and the ipsilateral retinotectal pathway was evaluated 4 or 8 days later, respectively. Results: Our data showed that, at different stages of development, a single IL-6 intravitreous treatment did not produce an inflammatory response and increased retinal axon innervation throughout the visual layers of the superior colliculus. Conclusions: Taken together, our data provide the first evidence that a single intravitreous injection with IL-6 leads to sprouting in the subcortical visual connections and suggest that small changes in IL-6 levels might be sufficient to impair the correct neuronal circuitry fine-tuning during brain development.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intravitreous Injection of Interleukin-6 Leads to a Sprouting in the Retinotectal Pathway at Different Stages of Development

Menezes

Goulart

Espírito-Santo³

et al. 2016

Neuroimmunomodulation

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“…Immunofluorescence was performed at PND11 on the animals as described before [18]. Briefly, retinal slices were pretreated with Triton X100 and incubated with a blocking solution of 1% BSA PBS 0.1 M. Slices were incubated overnight with anti-rabbitpSTAT6 (1: 100, Cell Signaling; #9361) or anti-rabbit-pERK (1: 1,000, Cell Signaling; #4377) primary monoclonal antibodies followed by Alexa Fluor 488 (1: 200, Invitrogen; #A21206) secondary antibody, diluted in PBS-BSA 1%, coverslipped using fluorescence medium (4% N-propylgalate in phosphate buffer/80% glycerol).…”

Section: Immunofluorescencementioning

confidence: 99%

“…Subcortical connections are sensitive to changes in the environment, and undergo anatomical reorganizations that lead to adaptive behavior and may serve as a substrate for cortical plasticity and functional recovery [17]. We have previously shown that the intravitreal delivery of proinflammmatory components, such as zymosan as well as either IL-2 or IL-6, result in a sprouting of retinotectal axons in different stages of development [18,19]. Thus, the aim of this study was to investigate the effect of an acute intravitreous injection of IL-4 on the activation of downstream signaling pathways in the retina and the consequences on the distribution of retinal axons in the subcortical visual nucleus.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Goulart¹,

Menezes²,

Espírito-Santo³

et al. 2018

Neuroimmunomodulation

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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.

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Peripheral Nervous System: Regenerative Therapies

Oliveira

Goulart

Lima

et al. 2016

Regenerative Medicine - From Protocol to Patient

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Intravitreous interleukin-2 treatment and inflammation modulates glial cells activation and uncrossed retinotectal development

Cited by 11 publications

References 77 publications

Intravitreous Injection of Interleukin-6 Leads to a Sprouting in the Retinotectal Pathway at Different Stages of Development

Intravitreous Injection of Interleukin-6 Leads to a Sprouting in the Retinotectal Pathway at Different Stages of Development

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Peripheral Nervous System: Regenerative Therapies

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