抄録
Nipradilol (NPR), anti-glaucoma drug, is a donor of nitric oxide (NO), blocks alpha and beta adrenoreceptors, and promotes axonal regeneration of axotomized retinal ganglion cells (RGCs) in cats. I examined either its NO supply or blocking the receptors promotes axonal regeneration of cat or rat RGCs. The left optic nerve (OpN) was cut 40-80 min after NPR- or blocker-injection. A peripheral nerve was sutured to the cut end. After 4-6 weeks, regenerated RGCs (R-RGCs) were labeled with different fluorescent dyes injected into the graft at 10 mm or 20 mm separately. RESULTS: An injection of NPR, 10(-7) M, increased numbers of regenerated RGCs (R-RGCs) into 13,884 (average, N=4) 6 week after the transplantation, comparing 3,470 (N=8) in no injected (control) retinas. Average ratio of R-RGCs with >=20 mm axon in R-RGCs with 10-20 mm axon, which implies axonal growth rate, was 83% in injected retinas, higher than in control retinas, 65%. Sodium nitroprusside (10(-5) M) injection increased numbers of R-RGCs into 6,585, 1.9 fold. None of adrenoreceptor blockers, plazosin (alpha-1), timolol (beta), or ICI-118,551 (beta-2) increased the number of R-RGCs nor 20R/10R ratios. Supporting this, R-RGCs numbers were not increased when carboxy-PTIO, NO-scavenger, was injected prior to NPR. NPR increased R-RGCs by 1.76 fold (4 wk) and 1.46 (5 wk) in the rat eye, indicating it has smaller effect on axonal regeneration of rat RGCs. CONCLUSIONS: Axonal regeneration of cat RGCs is promoted mainly by NO provided by NPR at very low concentration. Smaller effect of NPR on axonal regeneration of rat RGCs may be attributed to fewer population of beta cells. [Jpn J Physiol 54 Suppl:S165 (2004)]