IL-6 treatment increases the survival of retinal ganglion cells in vitro: The role of adenosine A1 receptor

Abstract

IL-6 is a pleiotropic cytokine classically denominated pro-inflammatory. It has been already demonstrated that IL-6 can increase the survival of retinal ganglion cells (RGC) in culture. In this work, we show that the trophic effect of IL-6 is mediated by adenosine receptor (A1R) activation. The neutralization of extracellular BDNF abolished the IL-6 effect and the treatment with IL-6 and CHA (an agonist of A1R) modulated BDNF expression as well as pCREB and pTrkB levels.

Adenosine A1Receptors Selectively Modulate Oxygen-Induced Retinopathy at the Hyperoxic and Hypoxic Phases by Distinct Cellular Mechanisms

“…Activation of retinal A 1 Rs has been shown to inhibit Ca2þ channels in retinal ganglion cells of mini-slices, 48,49 to protect NMDA-induced cell death in cultured retinal neurons, 50 and to mediate the IL-6 effect on the survival of cultured retinal ganglion cells. 51 Consistent with the A 1 R-mediated neuroprotective effect, early studies 28,52,53 indicate that cytotoxicity and cell death are generally more pronounced in neurons and astrocytes derived from A 1 R KO mice. Thus, additional studies are clearly warranted to clarify how A 1 R KO may confer cellular protection at the hyperoxic phase of OIR.…”

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

“…4). It has been well characterized that IL-6 increases the survival of RGCs in vitro [3,4,5] and in vivo [6,7]. However, the data presented here could not be explained by the increase in the RGC population or a delay in the elimination of transient connections since the treatment with IL-6 was performed on PND10 or PND30, when the main retinal programmed cell death [42,43,44] and retinotectal pathway refinement [18] had already occurred.…”

“…This interleukin increases the survival of retinal ganglion cells (RGCs) in culture [3,4,5] and also in an in vivo model of elevated ocular pressure [6,7]. Other studies have associated IL-6 to synaptic plasticity since endogenous IL-6 inhibition can prolong long-term potentiation and improve memory [8,9,10,11].…”

Retinal pigment epithelial cells display specific transcriptional responses upon TNF-α stimulation

“…ADORA1 , encoding the adenosine A1 receptor, is normally highly expressed in the eye, as well as in the brain, spinal cord and adrenal gland while lower expression levels are found in the colon, liver, kidney and skeletal muscle. ADORA1 expression in RPE cells has been related to neuroprotection of retinal ganglion cells and maintenance of aqueous humour homeostasis 23 24. Remarkably, the adenosine A1 receptor is activated by IL-6 and mediates the effect of IL-6 on retinal ganglion survival 24.…”