Different Effect of in Retinal Ganglion Cells Survival and Axon Regeneration.

The present study examines the role of in the initial response of retinal ganglion cells (RGCs) to axon damage and in optic nerve regeneration in mouse. Markers of retinal injury were identified using the normal retina database and optic nerve crush (ONC) database on GeneNetwork (www.genenetwork.org). One gene, , was highly upregulated following ONC. We examined the role of this transcription factor, , following ONC and optic nerve regeneration in mice. hybridization was performed using the Affymetrix 2-plex Quantigene View RNA Hybridization Tissue Assay System. was partially knocked out by intravitreal injection of AAV2-CMV-Cre-GFP in mice. Optic nerve regeneration model used knockdown. Mice were perfused and the retinas and optic nerves were dissected and examined for RGC survival and axon growth. was dramatically upregulated in the retina following ONC injury. The level of message increased by approximately eightfold 2 days after ONC. hybridization demonstrated low-level message in RGCs and cells in the inner nuclear layer in the normal retina as well as a profound increase in message within the ganglion cells following ONC. In retinas, partially knocking out significantly increased RGC survival after ONC as compared to the AAV2-CMV-GFP control group; however, it had little effect on the ability of axon regeneration. Combinatorial downregulation of both and resulted in a significant increase in RGC survival as compared to knockdown only. When was knocked down there was a remarkable increase in the number and the length of regenerating axons. Partially knocking out in combination with deletion resulted in a fewer regenerating axons. Taken together, these data demonstrate that is involved in the initial response of the retina to injury, playing a role in the early attempts of axon regeneration and neuronal survival. Downregulation of aids in RGC survival following injury of optic nerve axons, while a partial knockout of negates the axon regeneration stimulated by knockdown.