The neuropeptide NAP provides neuroprotection against retinal ganglion cell damage after retinal ischemia and optic nerve crush

Graefes Arch Clin Exp Ophthalmol. 2008 Sep;246(9):1255-63. doi: 10.1007/s00417-007-0746-7. Epub 2008 Apr 15.


Background: NAP, an 8-amino acid peptide (NAPVSIPQ=Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) derived from activity-dependent neuroprotective protein (ADNP), plays an important role in neuronal differentiation and the survival of neurons in different pathological situations. We already discovered that NAP increases the survival of retinal ganglion cells (RGC) in vitro, and supports neurite outgrowth in retinal explants at femtomolar concentrations. The aim of this study was to investigate the effects of NAP on RGC survival after transient retinal ischemia and optic nerve crush.

Methods: RGC of male Wistar rats were labelled retrogradely with 6 l FluoroGold injected stereotactically into both superior colliculi. Seven days later, retinal ischemia was induced by elevating the intraocular pressure to 120 mm Hg for 60 minutes or by crushing one optic nerve for 10 s after a partial orbitotomy. NAP was either injected intraperitoneally in the concentration of 100 microg/kg [corrected] 1 day before, directly after, and on the first and the second days after damage, or intravitreally (0.05 or 0.5 microg/eye) [corrected] directly after the optic nerve crush. Controls received the same concentrations of a control peptide. Densities of surviving RGC and activated microglial cells (AMC) were quantified in a masked fashion 10 days after damage by counting FluoroGold-labelled cells.

Results: After retinal ischemia, intraperitoneal injections of NAP increased the number of surviving RGC by 40% (p < 0.005) compared to the control group. After optic nerve crush, NAP raised the number of surviving RGC by 31% (p = 0.07) when injected intraperitoneally and by 54% (p < 0.05) when administered intravitreally.

Conclusions: NAP acts neuroprotectively in vivo after retinal ischemia and optic nerve crush, and may have potential in treating optic nerve diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Injections, Intraperitoneal
  • Ischemia / complications
  • Male
  • Nerve Crush
  • Neurites / physiology
  • Neuroprotective Agents / pharmacology*
  • Oligopeptides / pharmacology*
  • Optic Nerve Injuries / complications
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / etiology
  • Reperfusion Injury / prevention & control*
  • Retinal Diseases / etiology
  • Retinal Diseases / prevention & control*
  • Retinal Ganglion Cells / drug effects*
  • Retinal Vessels / pathology


  • Neuroprotective Agents
  • Oligopeptides
  • davunetide