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.
Department of Perinatology, Institute for Developmental Research, Kasugai, Aichi 480-0392, Japan. mwatanabe@inst-hsc.jp
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Watanabe
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Tokita
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Yata
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