Axonal regeneration of cat retinal ganglion cells is promoted by nipradilol, an anti-glaucoma drug.
Neurons in the CNS can regenerate their axons in an environment of the peripheral nervous system, but this ability is limited. Here we show that an anti-glaucoma drug, nipradilol, at low concentration led to a four-fold increase in the number of cat retinal ganglion cells regenerating their axons into a transplanted peripheral nerve 4 and 6 weeks after axotomy. Nipradilol also increased the number of three main regenerating retinal ganglion cell types (alpha, beta, not alpha/beta), and enhanced the rate of axonal regeneration of these retinal ganglion cells. Nipradilol is a donor of nitric oxide and an antagonist of alpha-1, beta-1 and -2 adrenoreceptors, and we therefore examined whether one of these pharmacological effects might be more important in promoting axon regeneration. A nitric oxide donor increased the number of regenerating retinal ganglion cells, but not the rate of axonal regeneration. Denitro-nipradilol (nitric oxide-deprived nipradilol) or a nitric oxide scavenger injected before nipradilol increased the number of regenerating retinal ganglion cells but did not promote regeneration rate. Blockade of individual alpha- and beta-adrenoreceptors did not increase the number of regenerating retinal ganglion cells or the rate of regeneration. From these results, it is suggested that nitric oxide plays a crucial role in mediating the effects of nipradilol on axon regeneration and neuroprotection, and the metabolite of nipradilol supports the effects.
Watanabe
M
M
Department of Perinatology, Institute for Developmental Research, Kasugai, Aichi 480-0392, Japan. mwatanabe@inst-hsc.jp
Tokita
Y
Y
Yata
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002415:Cats; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use; D009900:Optic Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020221:Optic Nerve Injuries / Q000188:drug therapy*; D010525:Peripheral Nerves / Q000637:transplantation; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D011412:Propanolamines; D011941:Receptors, Adrenergic; C036089:nipradilol