Neuroprotective activities of erythropoietin and rasagiline in experimental glaucoma model

Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell loss. Although the major risk factor is increased intraocular pressure, glaucoma related visual loss may occur even though the intraocular pressure is normal. The importance of neuroprotective treatment strategies in the glaucoma treatment is obvious. The aim of this study was to investigate the protective effects of erythropoetin and rasagiline on retinal ganglion cells by using biochemical and immunohistochemical methods in the presence of glaucomatous stress. In our study, 35 Sprague Dawley rats were randomly divided into 5 groups. The first group did not undergo surgery or medical intervention. The rats eyes in the other groups were induced for apoptosis with intravitreal N-methyl-D-aspartate injection. The second group was treated with intraperitoneal phosphate buffered saline (PBS), the third group oral saline (SF), the fourth group intraperitoneal erythropoetin and the fifth group with oral rasagiline. At the end of the experiment period, the right eyes of the rats were enucleated and blood samples were obtained. TUNEL analysis was performed on the retinal tissue samples obtained from the eyes of the rats and levels of nitric oxide synthase-2 (NOS-2), total oxidants and antioxidants (TOS-TAS), superoxide dismutase (SOD), brain derivered neurotrophic factor(BDNF) and irisin were also measured. Brain derivered neurotrophic factor(BDNF) and irisin levels were also measured in obtained blood samples. The percentages of apoptotic retinal ganglion cells in the PBS and SF treated groups was significantly higher than the first group (p <0.05). The percentages of apoptotic retinal ganglion cells in groups treated with erythropoetin and rasagiline were significantly lower than these the second and the third groups (p <0.05). Tissue levels of NOS-2, TOS, SOD, BDNF, and Irisin significantly increased in the eye specimens treated with PBS and SF (p <0,05). NOS-2, TOS, SOD levels decreased significantly (p <0,05) compared to the second and the third groups in rats treated with erythropoetin and rasajilin. There was no significant change in TAS level compared with the second and the third groups in rats treated with erythropoetin and rasagiline (p> 0.05). BDNF and Irisin levels were significantly increased in eyes treated with erythropoetin and rasagiline compared to the first group (p <0.05). The group treated with rasagiline showed a significant increase in BDNF level compared to the third group (p <0.05). When blood samples were investigated, there was no significant change in BDNF levels but results were consistent with eye samples at irisin levels. As a result, erythropoietin and rasagiline were found to be neuroprotective with neurotrophic effects and reducing NOS-2 expression. In addition, it was found that iris level in eye tissues increased in correlation with BDNF and at the same time tissue and blood levels were compatible. Key Words: expreimental glaucoma, excitotoxicity, erythropoietin, rasagiline