The Neuroprotective Effect Of GW2580 In Acute Intraocular Hypertension Glaucoma Model Mice

Objective:Microglia activation plays an important role in the development of neurodegenerative diseases such as glaucoma.Inhibiting microglia activation can protect the optic nerve.Therefore,it is of great significance to study the targeted inhibition of microglia activation in the treatment of glaucoma.The purposes of this study were to explore the protective effect of GW2580,a CSF1 R selective inhibitor,on RGCs and visual function by inhibiting microglia activation in acute intraocular hypertension glaucoma model mice.Methods:To establish acute intraocular hypertension glaucoma model.HE staining,Western blot,q PCR and immunofluorescence were used to detect retinal damage,the expression levels of CSF1 R and CSF1 and the activation of retinal microglia after acute pathogenic intraocular hypertension.Model mice were given GW2580 by oral administration(80mg/kg/d),and the inhibitory effects of GW2580 on CSF1 R signal and microglia activation were detected by immunofluorescence,western blot and q PCR.QPCR,HE staining,immunofluorescence,TUNEL and FVEP were used to evaluate the retinal neuroinflammation,RGCs damage and visual function after GW2580 intervention.Results:Retinal ischemia-reperfusion injury induced by acute high intraocular pressure glaucoma model in mice.The results of HE staining showed that the retinal thickness began to thin 24 h after modeling,approached the peak at 72 h,and stabilized at 7d.Western blot and q PCR results showed that the expression of CSF1 R and CSF1 increased most obviously 24 h after modeling.Meanwhile,immunofluorescence results showed that retinal microglia were activated in large quantities 24 h after modeling.Model mice were given GW2580 by oral administration for 3d、5d、7d,immunofluorescence results showed that GW2580 inhibited the activation of retinal microglia most significantly 5 days after gavage.Meanwhile,Western blot and q PCR results showed that the expressions of CSF1 R and CSF1 in the retina of model mice were down-regulated.After GW2580 intervention,the secretion of pro-inflammatory factors IL-1β,TNF-α and IL-6 decreased,the retinal thickness increased,the loss of RGCs decreased,the apoptosis index of RGCs decreased,and the latency of P1 and P2 waves of visual induced potential shortened,and the amplitude increased.Conclusion:GW2580 can inhibit the upregulation of CSF1 R signal and the activation of microglia induced by acute pathologically high intraocular pressure,alleviate the neuroinflammation of retina,reduce the loss and apoptosis of RGCs,improve visual function,and play a neuroprotective role in acute intraocular hypertension glaucoma model mice.