Abstract
Purpose::
The axons of retinal ganglion cells (RGCs) are directly affected by optic nerve trauma, stroke and glaucoma. NAP, an 8-amino acid peptide (NAPVSIPQ=Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) derived from activity-dependent neuroprotective protein, plays an important role for neuronal differentiation and the survival of neurons in different pathological situations. We previously found that NAP increases the survival of RGCs 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 optic nerve crush and transient retinal ischemia in adult rats.
Methods::
RGCs of male wistar rats were labeled retrogradely with FluoroGold injected stereotactically in both superior colliculi. Seven days later the optic nerve was crushed approximately 2 mm behind the eye for 10 seconds or retinal ischemia was induced by elevation of intraocular pressure to 120 mm Hg for 60 minutes. NAP (100µg/kg) was injected intraperitoneally one day before, direct after and on the first and the second day after the damage. The controls received the same concentration of a scrambled peptide, respectively. Densities of surviving RGCs and activated glia cells (AGCs) were quantificated ten days after damage by counting FluoroGold labeled cells in retinal whole mounts.
Results::
After retinal ischemia the number of surviving RGCs was increased up to 40.2% (p<0.005) compared to controls due to the intraperitoneal administration of NAP. AGCs were decreased by 45.5% (p<0.0005), respectively. After optic nerve crush, NAP increased the number of surviving RGCs by 30.6% (p=0.07), whereas the number of AGCs was decreased by 29.1% (p<0.0001). The number of RGCs and AGCs did show a significant correlation of -0,847 (p<0,0001).
Conclusions::
Intraperitoneal administration of the neuropeptide NAP supplies neuronal protection after optic nerve crush and retinal ischemia in vivo. These findings may help to find new therapeutic strategies since optic nerve diseases pose a major clinical problem and most of them cannot yet be treated successfully.
Keywords: neuropeptides • ganglion cells • cell survival