Is Saffron Able to Prevent the Dysregulation of Retinal Cytokines Induced by Ocular Hypertension in Mice?

José A Fernández-Albarral,Elena Salobrar-García,Miguel A Martínez-López,Inés López-Cuenca,Beatriz Martín-Sánchez,Ana I Ramírez,Juan J Salazar,Diego San Felipe,Eva M Marco,José M Ramírez,Meritxell López-Gallardo,María D Pinazo-Durán,Rosa De Hoz

doi:10.3390/jcm10214801

Abstract

Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.

Highlights

Glaucoma is a neurodegenerative disease in which there is an irreversible loss of retinal ganglion cells (RGCs), leading to blindness [1]
We demonstrated that following saffron treatment, most of the previously observed changes in the concentration of proinflammatory (IL-1β, IFN-γ, interleukin 6 (IL-6), and interleukin 17 (IL-17)) cytokines, anti-inflammatory cytokines (IL-4 and interleukin 10 (IL-10)), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and fractalkine in response to laser-induced ocular hypertension (OHT) [14] were absent
IL-1β, IL-6, IFN-γ, IL-17, TNF-α, interleukin 4 (IL-4), and fractalkine colocalize with microglia; IL-1β, TNF-α, VEGF, and BDNF colocalize with macroglia; and IL-10 colocalizes with axons of RGCs

Summary

Introduction

Glaucoma is a neurodegenerative disease in which there is an irreversible loss of retinal ganglion cells (RGCs), leading to blindness [1]. IOP control often fails to prevent the progression of the disease, so new factors that could be related to glaucomatous neurodegeneration, such as neuroinflammation, are being discovered [3,4]. In the course of the inflammatory process, retinal glial cells, both microglia and macroglia (Müller cells and astrocytes), can be activated and release factors that can be neuroprotective in some cases and neurodegenerative in others [5,6,7]. Activated microglia can be found along two extreme activation phenotypes, M1 and M2. The M2 phenotype releases neurotrophic factors (neurotrophins, Glial cell line-derived Neurotrophic Factor (GDNF), Brain-derived Neurotrophic Factor (BDNF), etc. The M2 phenotype releases neurotrophic factors (neurotrophins, Glial cell line-derived Neurotrophic Factor (GDNF), Brain-derived Neurotrophic Factor (BDNF), etc. and anti-inflammatory cytokines (TGFβ, IL-4, IL-10, etc.) that help control inflammation and promote neuronal survival

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