Protective Effect Of NGF Loaded PLGA Microspheres Combined With Ultrasonic Irradiation On The Rat Retinal Ganglion Cells Following The Optic Nerve Injury

Objective:To observe the protective effect of nerve growth factor(NGF) loaded ploy(lactic-co-glycolic acid)(PLGA) microspheres on retinalganglion cells(RGCs) following the optic nerve injury.Methods: The NGF-PLGA microspheres were made by usingPLGA,and the properties of microspheres were tested. Totally69SD adultmale rats were randomly divided into5groups: normal controlgroup(group A)、sham operated group (group B)、physiological salineinjection group(group C)、NGF injection group(group D) and NGF-PLGAinjection group(group E). Nine rats in groups A and B,17rats in groups C,D and E.All rats in groups B-E underwent ultrasound irradiation. Samplesof retinal section were collected for immunohistochemistry staining and HEstaining to observe the performance of glucose regulated protein78kDa(GRP78)and the pathological morphology change of retina of each group at12h and on the1st d、3rd d and7th d. Numbers of RGCs retrograde labeled by fluorogold(FG) before the operation was checked on the7th d.Results: The mean size of microsheres was (3.17±0.6) μm.Theencapsulation efficiency of NGF-PLGA microspheres was68.4%,theloading rate was0.0323%and the cumulative rate of drug-release on the7th d was82.6%.There were significant differences among5groups inRGCs count (F=65.858, P=0.000).There was no difference in RGCs countbetween group A and B (P=0.862>0.05), but had apparent differencesamong other groups were observed (P<0.05). Imunohistochemistry stainingshowed no positive cell in groups A or B. There were significantdifferences in GRP78positive rate of RGCs among groups C-E at differenttime points(Fgroup=184.330,Pgroup=0.000) and among each group at differenttime points(Ftime=21.472,Ptime=0.000).HE staining showed the retinaledema of group E was reduced on the7th d compared with that of groups Cand D.Conclusion:1、NGF loaded PLGA microspheres combined withultrasonic irradiation can improve the protective effect on RGCs after theoptic nerve injury.2、NGF can reduce the apoptosis of RGCs through theintervention of endoplasmic reticulum stress-induced apoptosis pathway.