Saffron benefits for eye diseases

Abstract

AbstractGlaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs). An increase in the intraocular pressure is the principal risk factor but controlling this pressure does not always prevent glaucomatous damage, so other harmful factors would be implicated in this pathologic process. Several mechanisms have been proposed that leads to the RGC death in glaucoma, including glutamate excitotoxicity, aggregation of misfolded proteins, mitochondrial dysfunction, oxidative stress, neurotrophic deprivation, and neuroinflammation, among others. Therefore, early diagnosis of neurodegeneration, understanding of its pathogenic mechanisms, and the development of new neuroprotective therapies represent major challenges for treating this disease.During the inflammatory process that occurs in glaucoma, retinal glial cells, both microglia and macroglia (Müller cells and astrocytes), become activated and release factors that can be neuroprotective in some cases and neurodegenerative in others. Cytokine‐ and chemokine‐mediated signalling engages in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Thus, a substance with anti‐inflammatory activity may protect against RGC degeneration.Increasing evidence from both experimental models and clinical studies in patients supports the neuroprotective effect of saffron components in neurodegenerative conditions and in retinal neurodegenerative pathologies, due to its important anti‐inflammatory, anti‐apoptotic, and antioxidant properties.This study investigated the neuroprotective and anti‐inflammatory effects of a hydrophilic saffron extract standardized to 3% crocin content in a mouse model of unilateral, laser‐induced ocular hypertension (OHT). For this purpose, morphological signs of microglial activation and the expression of P2RY12, which demonstrates the increased microglial activation, were analysed. In addition, the possible regulation of cytokine and myokine production was also studied. Treatment with saffron extract decreased microglial signs of activation including reduction of microglial cell numbers and morphological features of its activation, including decrease soma size and process retraction, both in OHT and in contralateral eyes. In addition, also partially reversed OHT‐induced down‐regulation of P2RY12 and prevented retinal ganglion cell death in OHT eyes. Furthermore, 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 in animals treated with saffron extracts. 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 this OHT glaucoma model in animals untreated with saffron, where microglial activation and down‐regulation of P2RY12 was more intense, and the significant changes in cytokine levels in both eyes in response to IOP increase were observed.All these findings indicate that oral administration of saffron extract could be beneficial in glaucoma by decreasing the neuroinflammation associated with increased intraocular pressure, reducing microglial activation, regulating the production of proinflammatory cytokines, VEGF, and fractalkine and preventing retinal ganglion cell death.