Neural Stem Cell-based Intraocular Administration of Pigment Epithelium-derived Factor Promotes Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Crush Injury in Rat: An Experimental Study

Background: pigment epithelium-derived factor (pedf) is regarded as a multifunctional protein possessing neurotrophic and neuroprotective properties. pedf has a very short halflife,and it would require multiple injections to maintain a therapeutically relevant level without a delivery system.however, multiple injections are prone to cause local damage or infection. to overcome this, we chose a cell-based system that provided sustained delivery of pedf and compared the effect of weekly injections of pedf and neural stem cell (nsc)-based intraocular administration of pedf on retinal ganglion cell (rgc) survival and axon regeneration after optic nerve injury.methods: seventy-two rats were randomly assigned to 3 groups:group with injections of phosphate buffered saline (pbs) (n=24),group with weekly injections of pedf (n=24), and group with nsc-based administration of pedf (n=24). western blot was used to analyze the pedf protein level 2 weeks after injection.retinal flat mounts and immunohistochemistry were employed to analyze rgc survival and axon regeneration 2 weeks and 4 weeks after injection. the data were analyzed with one-way anova in spss (version 19.0). a p<0.05 was considered significant.results: the pedf protein level in the group with nsc-based administration of pedf increased compared with that in the groups with injections of pedf and pbs (p<0.05). the pedfmodified nscs differentiated into gfap-positive astrocytes andβ-tubulin-iii-positive neurons. nsc-based administration of pedf effectively increased rgc survival and improved the axon regeneration of the optic nerve compared with weekly injections of pedf.conclusion: subretinal space transplantation of pedf-secreting nscs sustained high concentrations of pedf, differentiated into neurons and astrocytes, and significantly promoted rgc survival and axon regeneration after optic nerve injury.