Interleukin-2 and interleukin-4 increase the survival of retinal ganglion cells in culture

Sholl‐Franco, Alfred; Figueiredo, K G; Araújo, Elizabeth Giestal de

doi:10.1097/00001756-200101220-00029

Cited by 29 publications

(14 citation statements)

References 23 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%

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%

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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“…Understanding the endogenous mechanisms that minimize the pathological effects of increased mechanical strain on the neurons is a key target in preventing their loss in disease. Although aberrant immune signaling has been implicated in the pathogenesis of glaucoma (Tezel and Wax, 2004; Grus et al, 2008; Wax and Tezel, 2009; Križaj et al, 2014), certain cytokines have also been recognized for their ability to protect ganglion cells (Sholl-Franco et al, 2001; Sappington et al, 2006). It is tempting to propose that the increased expression of mRNA for IL-3 and IL-3Rα in eyes exposed to moderate IOP elevation may be part of an endogenous protective response, although this requires further confirmation.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective

Lim

Beckel

et al. 2016

Front. Cell. Neurosci.

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Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response. Mechanical stretch of isolated neurons was previously shown to trigger ATP release through pannexin hemichannels and autostimulation of P2X7 receptors (P2X7Rs) on the neural membrane. Given that P2X7Rs are linked to cytokine activation in other cells, this study investigates the link between neuronal stretch and cytokine release through a P2X7-dependent pathway. Cytokine assays showed application of a 4% strain to isolated rat retinal ganglion cells (RGCs) released multiple cytokines. The P2X7R agonist BzATP also released multiple cytokines; Interleukin 3 (IL-3), TNF-α, CXCL9, VEGF, L-selectin, IL-4, GM-CSF, IL-10, IL-1Rα, MIP and CCL20 were released by both stimuli, with the release of IL-3 greatest with either stimuli. Stretch-dependent IL-3 release was confirmed with ELISA and blocked by P2X7R antagonists A438079 and Brilliant Blue G (BBG), implicating autostimulation of the P2X7R in stretch-dependent IL-3 release. Neuronal IL-3 release triggered by BzATP required extracellular calcium. The IL-3Rα receptor was expressed on RGCs but not astrocytes, and both IL-3Rα and IL-3 itself were predominantly expressed in the retinal ganglion cell layer of adult retinal sections, implying autostimulation of receptors by released IL-3. While the number of surviving ganglion cells decreased with time in culture, the addition of IL-3 protected against this loss of neurons. Expression of mRNA for IL-3 and IL-3Rα increased in rat retinas stretched with moderate intraocular pressure (IOP) elevation; BBG blocked the rise in IL-3, implicating a role for the P2X7R in transcriptional regulation in vivo. In summary, mechanical stretch triggers release of cytokines from neurons that can convey neuroprotection. The enhancement of these signals in vivo implicates P2X7R-mediated IL-3 signaling as an endogenous pathway that could minimize damage following neuronal exposure to chronic mechanical strain.

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“…Relatively low concentration of the muscarinic receptor agonist carbamycholine was found to significantly increase the survival of retinal neurons via M1 muscarinic receptors (Pereira et al 2001). Also, IL-4 increased the survival of retinal neurons mediated by the activation of M1 muscarinic receptors (Sholl-Franco et al 2001). Directly depending on M1 muscarinic receptor activation, cAMP played an important role in controlling the survival of retinal neurons (Santos and Araujo 2001).…”

Section: Introductionmentioning

confidence: 94%

Neuroprotection of Muscarinic Receptor Agonist Pilocarpine Against Glutamate-induced Apoptosis in Retinal Neurons

Zhou

Zhu

et al. 2008

Cell Mol Neurobiol

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Neuroprotection offers potential as an alternative therapy for glaucoma. Pilocarpine, as a typical muscarinic receptor agonist, remains among the major intraocular pressure lowering drugs for the conventional treatment of glaucoma. However, whether pilocarpine also possesses neuroprotection against glutamate cytotoxicity in retinal neurons is still unknown. In rat primary retinal cultures, identification of neuron, cell viability, apoptosis, intracellular Ca(2+) concentration, mitochondrial membrane potential, gene expression were studied by immunofluorescence, MTT, High Content Scanning, confocal microscopy, reverse-transcription PCR, and western blot analysis, respectively. Pretreatment of pilocarpine could prevent glutamate-induced neuron death, which was blocked by the non-selective antagonist atropine and the M1-selective muscarinic receptor antagonist pirenzepine. The antiapoptotic effect of pilocarpine was associated with maintaining calcium homeostasis, recovering mitochondrial membrane potential, and regulating the expression of Bcl-2 and Caspase-3. These studies demonstrated that pilocarpine had effective protection against glutamate-induced neuronal apoptosis through M1 muscarinic receptor. The results may provide an insight into the new mechanism of glaucoma therapy that pilocarpine may potentially act as a retinal neuroprotectant.

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Interleukin-2 and interleukin-4 increase the survival of retinal ganglion cells in culture

Cited by 29 publications

References 23 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

Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective

Neuroprotection of Muscarinic Receptor Agonist Pilocarpine Against Glutamate-induced Apoptosis in Retinal Neurons

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