Pigment-epithelium-derived factor down regulates hyperglycemia-induced apoptosis via PI3K/Akt activation in goat...

Pigment epithelium-derived factor (PEDF) is a well-known protease inhibitor for angiogenesis in the eye, suggesting that loss of PEDF in eye is implicated in the pathogenesis of proliferative diabetic retinopathy. Since the role of PEDF in diabetic retinopathy is unclear, the effect of PEDF on different types of cells constituting the blood vessel has to be checked. Here, we have investigated the effects of PEDF under hyperglycemic conditions in retinal pericytes, isolated from goat's eye and used to analyze the signaling pathway involved. High glucose increased the apoptotic cell death and intracellular reactive oxygen species generation, which was blocked on the addition of PEDF. PEDF was found to inhibit the apoptotic cell death and protect the cells via activating the PI3K/Akt pathway, which was analyzed with dominant negative Akt and constitutively active Akt-transfected cells. These results demonstrate that PEDF protects pericytes against the high glucose-induced apoptosis and dysfunction.