IL-6, A1 and A2aR: A crosstalk that modulates BDNF and induces neuroprotection

Abstract

Several diseases are related to retinal ganglion cell death, such as glaucoma, diabetes and other retinopathies. Many studies have attempted to identify factors that could increase neuroprotection after axotomy of these cells. Interleukin-6 has been shown to be able to increase the survival and regeneration of retinal ganglion cells (RGC) in mixed culture as well as in vivo. In this work we show that the trophic effect of IL-6 is mediated by adenosine receptor (A2aR) activation and also by the presence of extracellular BDNF. We also show that there is a complex cross-talk between IL-6, BDNF, the Adenosine A1 and A2a receptors that results in neuroprotection of retinal ganglion cells.

HGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease

“…We focused on secretory factors expressing the strongest signal (Figure 4B), and combined this with bioinformatics analysis and literature search to analyze the role of each factor in detail (data not shown); we then selected four potential factors including IL‐6, HGF, ANG, and sgp130, which may be involved in damage repair. [ 42–46 ] With the mature and stable OA‐induced damage model in vitro, several key indexes were investigated to analyze and compare the repair features of the four factors. We observed that only HGF substantially ameliorated neural cell damage (Figure S5, Supporting Information) in multiple ways, including dendritic length and mitochondrial function.…”

Protective Efficacy of a Dietary Supplement Based on Forskolin, Homotaurine, Spearmint Extract, and Group B Vitamins in a Mouse Model of Optic Nerve Injury

“…Once activated after optic nerve damage, as in the ONC model or after IOP increase as in the inherited glaucoma mouse model, glial cells become hypertrophic and induce the activation of NF-κB, which promotes the early release of pro-inflammatory cytokines, including IL-6, and the accumulation of inflammatory mediators such as iNOS [8,47]. Interestingly, inflammatory cytokines have been also shown to promote RGC survival [48][49][50], in line with the notion that both reparative and pathogenic factors coexist in the inflammatory microenvironment [51]. In glaucoma, in particular, early stages of the disease are characterized by protective effects of the inflammatory response [52].…”

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].…”