Neuroprotective Effect Of Geranylgeranylacetone On Retinal Ganglion Cells In Rats With Acute Intraocular Hypertension

Objective Glaucoma, one of the world's leading causes of blindness, is characterized by the atrophy of optic disc and characteristic defect of visual field. It has been postulated that apoptosis, a highly regulated process of cell death, is the final common pathway for retinal ganglion cells (RGCs). death in glaucoma. Intervening with drugs or other means, so that which are not damaged, or only partially damaged, or in a toxic environment near death of retinal cells can survive or prolong the survival time is of great significance. Heat shock protein 70 (HSP70) has been proved to be resistant to ischemia and seizures, which suggests that HSP70 is important for neuroprotection. In the experiment, we made a rat model of acute intraocular hypertension to study the effects of geranylgeranylacetone (GGA) on the expression of HSP70 and on RGCsMethod Sixty healthy SD rats were randomly divided into three groups, 20 rats for healthy control group (Group A),20 rats for acute intraocular hypertension group(Group B),20 rats for GGA pretreatment group(Group C). Group A and group B were given oral treatments of saline. Group C were given oral treatments of GGA. After a week, group B and group C were induced by acute intraocular hypertension model, Group A without any intervention. After 6h,24h,48h,72h animals were killed and removed the eyes. Put the eyes in the bottles containing 10% neutral formaldehyde. The eyes were embedded in paraffin, sliced. HE staining,the histological changes in retina of different time after reperfusion were observed by light microscopy. The expression of heat shock protein 70(HSP70) and Cysteine-containing aspartate-specific proteases-3 (caspase-3) at specified times was determined by immunohistochemistry. The expression of positive results is the cytoplasm or the nucleus stained yellow or brown. Using SPSS 16.0 statistical software, independent samples t test was carried out, P <0.05 indicated significant difference.Result Group A had normal retinal structure all the time. Comparing with group B, group C's retinal was mild edema. The retinal inner layer thickness of group C was greater than that of the group B during all the period. In group B,a few of HSP70 positive cells were found 6 hour after process and increased gradually until reaching the peak 24 hours later and then decreased gradually. The amount of HSP70 positive cells increased in group C at all time courses, and the difference of the amount of HSP70 positive cells between group B and group C was significant (P< 0.05). In group B, a few of caspase-3 positive cells were found 6 hour after process, and increased gradually until reaching the peak 24 hours later and after 48h decreased gradually. Few caspase-3 positive cells were found 72 hours after reperfusion. The amount of caspase-3 positive cells decreased in group C at all time courses, and the difference of the amount of caspase-3 positive cells between group B and group C was significant (P< 0.05).Conclusion Acute intraocular hypertension can cause optic nerve ischemia, retinal edema, RGCs apoptosis and HSP70 expression in the retina. GGA can induce HSP70 expression in the retina and protect RGCs from acute intraocular hypertension in a rat model...