The antioksidant effect of edaravone and ellajic acid on N- methyl-N-nitrosourea induced retinitis pigmentosa model

Retinitis pigmentosa, which may begin in childhood and result in blindness, is the most common hereditary retinal dystrophy. In this study, it was aimed to search protective effects of Edaravon and Ellajic acid on photoreceptor cell apoptosis through biochemical and histological methods and within the scope of experimental retinitis pigmentosa model induced with N-Methyl-N-Nitrosurea. At the beginning of the study 49 Spraque Dawley rats were divided into seven equal groups randomly. The first group is designated as control group and no surgery or medical treatment was performed to the rats within this group. For rats included in the other groups, photoreceptor cell apoptosis was induced by injecting intraperitoneal N-Methyl-N-Nitrosurase. Within the aspect of performed treatment to other groups that designated as sham groups; the second and third groups were treated with intraperitoneal PBS, the fourth and fifth groups were treated with intraperitoneal Edaravon and the sixth and seventh groups were treated with intraperitoneal Ellajic acid. The first, second, fourth and sixth groups were decapitated on the 3rd day whereas the third, fifth and seventh groups were on the 7th day. The eyes were enucleated and retinal tissue was removed. For the retinal tissue samples that were taken from right eyes; apoptotic index measurement was made by TUNEL staining, retinal thickness measurement was made by H&E staining and rodopsin immunoreactivity was examined by immunohistochemical staining whereas for the retinal tissue samples of left eyes; Bax and Bcl 2 analyzes were performed by applying ELISA methodology. According to the comparison made between sham group and control group, it was seen that the sham group had higher mean Bax values, lower Bcl 2 values, higher percentage of apoptotic index, lower rhodopsin immunoreactivity and a statistically significant thinning at the outer nuclear layer (p <0.05). On the other hand, the comparison made between Sham 1 and Sham 2 groups lead to the conclusion that Sham 1 group, based on mean values, had higher Bax values, lower Bcl 2 values, higher percentage of apoptotic index (measured by TUNEL staining) and statistically significant thinning at the outer nuclear layers (p<0.05). When Edaravone and Ellajic acid groups were compared to sham group at the end of 3rd day based on mean values, Bcl 2 values were high, Bax values were low and percentage of apoptotic index measured by TUNEL staining was found as statistically low (p<0.05). Rodopsin immunoreactivity, outer nuclear layer thickness, outer nuclear layer / total retinal thickness ratio were found significantly higher in the Edaravone group than the sham groups at the end of 3rd and 7th days (p <0.05). For the Ellajic acid group, at the end of 3rd and 7th days, rodopsin immunoreactivity, outer nuclear layer thickness, outer nuclear layer / total retinal thickness ratio were found to be higher than sham groups but it wasn't statistically significant (p> 0.05). Edaravone and Ellajic acid may be a therapeutic agent for RP patient. Further studies are needed to demonstrate the possible effects of these agents in humans, which detect inhibitory effects of photoreceptor cell apoptosis in the experimental RP model. Key Words: N-Methyl-N-Nitrosurea, experimental retinitis pigmentosa, Edaravone, Ellajic acid