Intraocular injection of dibutyryl cyclic AMP promotes axon regeneration in rat optic nerve

Nicholas T. Monsul, Abram R. Geisendorfer, Paul J. Han, Rudrani Banik, Mary Ellen Pease, Richard Skolasky, Paul N. Hoffman

Research output: Contribution to journalArticle

Abstract

The optic nerve is a CNS pathway containing molecules capable of inhibiting axon elongation. The growth program in embryonic retinal ganglion cell (RGC) neurons enables axons to regenerate in the optic nerve through at least two mechanisms. Namely, high cyclic AMP (cAMP) levels abrogate the ability of CNS molecules to inhibit elongation, and the pattern of gene expression enables axons to undergo rapid, sustained, and lengthy elongation. In adult mammals, recovery of visual function after optic nerve injury is limited by both the death of most RGC neurons and the inability of surviving axons to regenerate. We now report that a single intraocular injection of the membrane-permeable cAMP analogue dibutyryl cAMP (db cAMP) promotes the regeneration of RGC axons in the optic nerves of adult rats, but does not prevent the death of RGC neurons. This regeneration in optic nerves crushed within the orbit (2 mm from the eye) was equally effective either 1 day before or 1 day after db cAMP injection. The number of regenerating axons, which was maximal 14 days after crush, declined with increasing time after injury (i.e., 28, 56, and 112 days) and distance beyond the crush site (i.e., 0.25, 0.5, and 1.0 mm). Thus, db cAMP promotes optic nerve regeneration without increasing the survival of axotomized RGC neurons. Furthermore, since db cAMP does not enable axons to undergo rapid, sustained, and lengthy elongation, strategies that increase survival and promote these changes in elongation may critically complement the ability of db cAMP to promote regeneration.

Original languageEnglish (US)
Pages (from-to)124-133
Number of pages10
JournalExperimental Neurology
Volume186
Issue number2
DOIs
StatePublished - Apr 2004

Fingerprint

Intraocular Injections
Bucladesine
Optic Nerve
Axons
Regeneration
Retinal Ganglion Cells
Neurons
Cyclic AMP
Optic Nerve Injuries
Nerve Regeneration
Recovery of Function
Orbit
Mammals
Gene Expression
Injections
Membranes
Wounds and Injuries
Growth

Keywords

  • Axon elongation
  • Axon regeneration
  • Axotomy
  • CNS regeneration
  • Dibutyryl cyclic AMP
  • Optic nerve injury
  • Rat optic nerve
  • Retinal ganglion cell

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Intraocular injection of dibutyryl cyclic AMP promotes axon regeneration in rat optic nerve. / Monsul, Nicholas T.; Geisendorfer, Abram R.; Han, Paul J.; Banik, Rudrani; Pease, Mary Ellen; Skolasky, Richard; Hoffman, Paul N.

In: Experimental Neurology, Vol. 186, No. 2, 04.2004, p. 124-133.

Research output: Contribution to journalArticle

Monsul, Nicholas T. ; Geisendorfer, Abram R. ; Han, Paul J. ; Banik, Rudrani ; Pease, Mary Ellen ; Skolasky, Richard ; Hoffman, Paul N. / Intraocular injection of dibutyryl cyclic AMP promotes axon regeneration in rat optic nerve. In: Experimental Neurology. 2004 ; Vol. 186, No. 2. pp. 124-133.
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