Neuroprotective effects of papaverine on retinal ganglion cells in optic nerve transection model

Abstract

Papaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm and vasospasm. It is also known as a specific inhibitor of phosphodiesterase (PDE) 10A. In striatonigral and striatopallidal neurons, inhibition of PDE 10A by papaverine activated cAMP/PKA signal cascade. This study was aimed to investigate the effects of papaverine on the survival of retinal ganglion cells in rat optic nerve transection model. After intraorbital optic nerve (ON) crush of the right eye, 2 µl of BSS or 50, 200, 500 µg/ml papaverine was injected to vitreous cavity in the injured eye. At 2 or 7 days after the insult, retina samples were collected for retinal ganglion cell (RGC) count and immunohistochemistry analysis. At seven days, comparing to the BSS control group, RGC density of the 500 µg/ml group showed significant increased survival of RGC. Immunoreactivity of phosphorylated-cAMP response element binding protein (p-CREB) was not detectable in the BSS control group. Increased expression of p-CREB was detected in the RGC layer and inner neuclear layer of the papavarine treated groups at both 2 and 7 days groups. Our result showed that papaverine was neuroprotective to RGC when their axons were transected in the crush model. This effect might be through up-regulation of the p-CREB.