Neuroprotective effect of nipradilol on axotomized rat retinal ganglion cells

Toru Nakazawa, Hiroshi Tomita, Katsuhiro Yamaguchi, Yumi Sato, Masahiko Shimura, Soichiro Kuwahara, Makoto Tamai

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Purpose. To determine whether nipradilol, a new anti-glaucoma drug, can protect retinal ganglion cells (RGCs) from secondary cell death caused by transection of the optic nerve (ON). Methods. The ON was transected 0.7 mm from its exit from the eye in Sprague Dawley rats. Nipradilol (1 × 10-8 - 10-3 M), timolol, prazosin, or sodium nitroprusside (SNP) (1 × 10-6 - 10-4 M) was injected intravitreally fifteen-minutes before the ON transection. Control eyes received the same amount of phosphate buffered (PB). The RGCs were labeled retrogradely by placing gelfoam soaked in fluoro-gold (FG) on the stump of ON. RGCs density was determined by counting the FG-labeled RGCs in flat-mounted retinas 3 to 14 days post-transection. To determine whether the neuroprotective action of nipradilol was due to its NO-donor property, carboxy-PTIO, a NO-scavenger, or KT5832, a protein kinase G inhibitor, was injected with the nipradilol. Results. After ON transection, the number of surviving RGCs after intravitreal injection of 1 × 10-4 M nipradilol was significantly higher than that following PB injection. This protective activity was dose-dependent. Neither timolol nor prazosin had a neuroprotective effect but SNP protected RGCs in a dose-dependent manner. Carboxy-PTIO and KT5832 decreased the neuroprotective effect of nipradilol. Conclusions. These results indicate that nipradilol has a possibility of neuroprotective effect on axotomized RGCs, and the effect depended mainly on its NO-donor property.

Original languageEnglish
Pages (from-to)114-122
Number of pages9
JournalCurrent Eye Research
Volume24
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Axotomy
  • Ganglion cell
  • Glaucoma
  • Nipradilol
  • Nitric oxide

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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