Neuroprotective effects of nipradilol on purified cultured retinal ganglion cells.

Abstract

To investigate effects of nipradilol, a nonselective beta- andbgr;-and selective alpha1-receptor antagonist and a potential nitric oxide releaser, on retinal ganglion cells purified and cultured in a serum-free medium. Retinal ganglion cells were isolated from 2-day-old Sprague-Dawley rats by means of two-step panning. A series of nipradilol (10(-5), 10(-6), 10(-7), 10(-8), 10(-9), and 10(-10)-mol/L) or vehicle solutions were administered to the culture medium for 48 hours, and the survival rate of retinal ganglion cells was evaluated using a newly developed system that evaluates the survival rate in small and large retinal ganglion cells separately. The effects of timolol maleate or bunazosin (10(-5), 10(-6), 10(-7), and 10(-8) -mol/L) solutions on retinal ganglion cells survival were also evaluated. The survival rate was evaluated after 10(-5)-mol/L c-PTIO (2-[4-carboxyphenyl]-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide potassium salt), a nitric oxide scavenger, was administered to retinal ganglion cells with 10(-5)-mol/L nipradilol. Nipradilol significantly increased the survival rate of both small and large retinal ganglion cells in a concentration-dependent manner compared with the controls. The maximum survival rate improvement of small and large retinal ganglion cells was 29.1% and 14.5%, respectively. Although timolol maleate and bunazosin did not affect the survival rate, 10(-5)-mol/L c-PTIO significantly inhibited the nipradilol-induced survival rate improvement by 69.9% in small retinal ganglion cells and by 91.6% in large retinal ganglion cells. Nipradilol improves the survival rate of cultured postnatal rat retinal ganglion cells, and the nitric oxide generated from nipradilol may contribute to this effect.