Increased expression of phosphorylated c-Jun and phosphorylated c-Jun N-terminal kinase associated with neuronal cell death in diabetic and high glucose exposed rat retinas.

The aim of this study is to examine whether the increased expression of phosphorylated c-Jun (p-c-Jun) and phosphorylated c-Jun N-terminal kinase (p-JNK) are significantly associated with neuronal cell death in diabetic rat retinas and retinas exposed to high glucose. Retinas isolated from six adult male Sprague-Dawley rats and six streptozotocin-induced diabetic rats (DM) were cultured in serum-free medium. The explants from non-diabetic controls were cultured in normal-glucose (N) or high-glucose (HG) medium. Furthermore, neurotrophin-4 (NT-4) and Taurine-conjugated ursodeoxycholic acid (TUDCA) were incubated in HG medium. After 7 days, the numbers of regenerating neurites were counted per explant. After counting, the explants were fixed, cryosectioned, and stained by TUNEL, and also immunostained for p-c-Jun and p-JNK. The numbers of TUNEL-positive, p-c-Jun- and p-JNK-immunopositive cells in the GCL were significantly higher and the numbers of regenerating neurites were significantly lower in the HG and the DM groups than in the N groups. In the HG groups supplemented with NT-4 and TUDCA, the numbers of TUNEL-positive, p-c-Jun- and p-JNK-immunopositive cells were significantly lower and the numbers of neurites were significantly higher than in the HG group without NT-4 and TUDCA. Increased expression of p-c-Jun and p-JNK is associated with neuronal cell death in diabetic rat retinas and retinas exposed to high glucose. Neuroprotective effect of TUDCA and NT-4 is correlated with the suppression of p-c-Jun and p-JNK expression. These results provide a better understanding of the neurodegenerative process underlying DR.