Study On The Protective Effect Of Hepatocyte Growth Factor On Optic Nerve Of Primary Open-angle Glaucoma And Its Mechanism

Objective To examine if c-met-receptor-activation by HGF can promote retinal ganglion cell survival and regeneration and the possible mechanism of neuroprotective effects by HGF in a chronic glaucoma rat model.Methods SD rats were randomly divided into three groups: normal control group,chronic intraocular hypertension group and chronic intraocular hypertension HGF-injection group.Chronic glaucoma model was made in Sprague Dawley rats by cauterizing three episcleral veins;animals were examined for changes in intraocular pressure by a i Care tonometer.HGF was injected immediately at a dosage of 4ug intravitreally after cauterizing episcleral veins.The levels of HGF in anterior chamber were measured by ELISA.The cellular distribution of c-Met in the retina were examined by anti-c-Met and immunostaining.Apoptosis of retinal ganglion cells were visualized by terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL)staining.Changes in the expression pattern of Akt,p-Akt,Bcl-2 and Bcl-xl were determined by Western blotting.Results As early as after surgery,there was a significant increase in intraocular pressure,and maintained up to 2 weeks.Compared with the normal group,the levels of HGF in the anterior chamber of rats with high intraocular pressure was significantly increased.Compared with the chronic intraocular hypertension group,the TUNEL-labeled RGC in HGF-injection group was significantly decreased,the difference was statistically significant(P<0.05).In the retina,c-Met was expressed mainly in cells in the ganglion cell.In retinal samples,compared with the normal control group,p-Akt,Bcl-2 and Bcl-xl expressions were significantly downregulated in ocular hypertensive eyes(P<0.05),while upregulated in the HGF-treated animals compared with high intraocular pressure rats(P<0.05).Conclusion HGF may play a protective role in chronic ocular hypertension by activating the Akt signaling pathway and increasing its downstream antiapoptotic protein expression.HGF can inhibit the apoptosis of glaucomatous ganglion cells and HGF may become a potential drug for the treatment of glaucoma.It provides a new therapeutic approach to prevent glaucoma damage to the visual field.