Neuroprotective effects of nipradilol on purified cultured retinal ganglion cells

J Glaucoma. 2002 Jun;11(3):231-8. doi: 10.1097/00061198-200206000-00012.

Abstract

Purpose: 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.

Conclusion: Nipradilol improves the survival rate of cultured postnatal rat retinal ganglion cells, and the nitric oxide generated from nipradilol may contribute to this effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Animals, Newborn
  • Antihypertensive Agents / pharmacology*
  • Cell Separation
  • Cell Survival / drug effects
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Cyclic N-Oxides / pharmacology
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Imidazoles / pharmacology
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Propanolamines / pharmacology*
  • Quinazolines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells / drug effects*
  • Timolol / pharmacology

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Culture Media, Serum-Free
  • Cyclic N-Oxides
  • Imidazoles
  • Neuroprotective Agents
  • Propanolamines
  • Quinazolines
  • 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
  • Nitric Oxide
  • Timolol
  • bunazosin
  • nipradilol