Protective effects of placental growth factor on retinal neuronal cell damage.

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family. Although it has been reported that PlGF protects against neuronal damage in the brain, little is known about the effects of PlGF in the retina. Therefore, we investigated the effects of PlGF on retinal neuronal cells. To evaluate the effects of PlGF against L-buthionine-(S,R)-sulfoximine (BSO)/glutamate cell death, oxygen-glucose deprivation (OGD)-induced cell death, and light-induced cell death, RGC-5 and 661W cells were used. We evaluated the mechanism responsible for the protective effects of PlGF against retinal neuronal cell death by performing the examinations with U1026, which is a mitogen-activated protein kinase (MEK) inhibitor, and LY294002, which is a phosphoinositide 3-kinase (PI3K) inhibitor. In addition, we measured caspase-3/7 activity in RGC-5 cells and 661W cells. PlGF protected against RGC-5 cell death induced by BSO/glutamate and OGD and against 661W cell death induced by light irradiation. Moreover, an anti-PlGF antibody negated these protective effects. The protective effects of PlGF against OGD-induced RGC-5 cell death and light-induced 661W cell death were suppressed by using an anti-PlGF antibody, U1026, and LY294002. Treatment with PlGF suppressed caspase-3/7 activity in both cell lines. We demonstrated for the first time that PlGF exerts a protective effect by inhibiting the activation of caspase-3/7 through the MEK and PI3K pathway in retinal neuronal cells. These data suggest that PlGF may be an important protective factor in the retina.