Effect of lithium chloride on n-methyl-n-nitrosure-induced retinal degeneration in rats

The efficacy of lithium chloride (LiCl) was investigated against retinal degeneration induced by N-Methyl-N-Nitrosurea (MNU) in rats. A total of 108 rats were divided into 6 groups (18 rats per group). Control (Group 1), MNU at the dose of 80 mg/kg was injected intraperitoneally once to the MNU (Group 2) and treatment groups (Group 3 and 4). LiCl was administered intraperitoneally to the treatment groups at the doses of 30 mg/kg (Group 3) and 60 mg/kg (Group 4) once a day until euthanizia, starting the day before MNU administration. The rats in the 5th and 6th groups were only injected with 30 and 60 mg/kg LiCl, respectively. After the 2, 7, and 14 days of the MNU injection, 6 rats from each group were euthanized, and the eyes were enucleated. After the routine procedures, the eyes were examined using histopathological, immunohistochemical (Caspase-3, Caspase 6, Bcl-2, Bax, 8-OHdG, Red-Green opsin, rhodopsin), TUNEL, and Western Blot (GFAP, BDNF, GSK 3β) methods. At the end of the 2nd day, the outer nuclear layer (ONL) of the MNU group was significantly thinner than the treatment groups (P<0.05), and the apoptotic index of the cells in the ONL was higher than the other groups (P<0.05). However, no significant difference was found between the treatment groups (P>0.05). Caspase-3, Caspase-6, Bax, and 8-OHdG immunoreactivities significantly increased in the MNU group compared to the treatment groups (P<0.05). Besides, Bcl-2, Red-Green opsin, rhodopsin immunoreactivities significantly decreased in the MNU group compared to the treatment groups (P<0.05). In Western Blot analysis; GFAP expressions significantly increased in the MNU group, whereas BDNF expression increased in the 30 and 60 mg/kg LiCI treated groups compared to the others (P<0.05). Furthermore, GSK-3β increased in the MNU group compared to the other groups (P<0.05). On the 7th and 14th days, approximately 90% thinning was observed in the retinal ONL in the MNU treated rats compared to the untreated rats, while a 70% thinning was observed in the MNU+LiCI treated rats. These thinnings were found to be significant (P<0.05). According to the immunohistochemical staining of rhodopsin and red-green opsin, no staining was observed in the MNU group, whereas staining was observed in the cells that survived in the MNU+LiCI groups. In Western Blot Analysis, BDNF expression significantly increased in the LiCI groups compared to the MNU, while GSK-3β increased significantly in the MNU group compared to the others. In conclusion; LiCl treatment was partially effective in preventing retinal degeneration in MNU-induced model, and exerted its effects by increasing BDNF, and decreasing GSK-3β levels.