Neuroprotective effects of nipradilol on purified cultured retinal ganglion cells.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Nipradilol improves the survival rate of cultured postnatal rat retinal ganglion cells, and the nitric oxide generated from nipradilol may contribute to this effect.
Department of Ophthalmology, Yamanashi Medical University, Tamaho Yamanashi, Japan. kenjik@res.yamanashi-med.ac.jp
Kenji
K
Kashiwagi
Yoko
Y
Iizuka
Shigeo
S
Tsukahara
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007093:Imidazoles / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D013999:Timolol / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D016895:Culture Media, Serum-Free; D003497:Cyclic N-Oxides; D007093:Imidazoles; D018696:Neuroprotective Agents; D011412:Propanolamines; D011799:Quinazolines; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D013999:Timolol; C018176:bunazosin; C036089:nipradilol