Transformation of adult retina from the regenerative to the axonogenesis state activates specific genes in various subsets of neurons and glial cells.

The purpose of this study was to identify the gene expression profile of the regenerating retina in vitro. To achieve this goal, three experimental groups were studied: (1) an injury control group (OC-LI group) that underwent open crush (OC) of the optic nerve and lens injury (LI) in vivo; (2) an experimental group (OC-LI-R group) that comprised animals treated like those in the OC-LI group except that retinal axons were allowed to regenerate (R) in vitro; and (3) an experimental group (OC-LI-NR group) that comprised animals treated as those in the OC-LI group, except that the retinas were cultured in vitro with the retinal ganglion cell (RGC) layer facing upwards to prevent axonal regeneration (NR). Gene expression in each treatment group was compared to that of untreated controls. Immunohistochemistry was used to examine whether expression of differentially regulated genes also occurred at the protein level and to localize these proteins to the respective retinal cells. Genes that were regulated belonged to different functional categories such as antioxidants, antiapoptotic molecules, transcription factors, secreted signaling molecules, inflammation-related genes, and others. Comparison of changes in gene expression among the various treatment groups revealed a relatively small cohort of genes that was expressed in different subsets of cells only in the OC-LI-R group; these genes can be considered to be regeneration-specific. Our findings demonstrate that axonal regeneration of RGC involves an orchestrated response of all retinal neurons and glia, and could provide a platform for the development of therapeutic strategies for the regeneration of injured ganglion cells.