SOCS3 and Optic Nerve Regeneration in Zebrafish

Glaucoma often leads to blindness due to optic nerve damage and retinal ganglion cell death. Optic nerve regeneration may restore vision in patients suffering from glaucoma. Unfortunately the damaged mammalian optic nerve does not readily regenerate. Interestingly, fish regenerate their optic nerve following damage and therefore provide an ideal system for studying the mechanisms underlying successful optic nerve regeneration. In a recent screen for genes that might mediate successful optic nerve regeneration in zebrafish, Dr. Goldman has identified suppressor of cytokine signaling 3 (SOCS3), which is highly induced in retinal ganglion cells that are regenerating their optic axons. SOCS3 is a multifunctional SOCS protein that not only modulates the immune response, but can also influence a number of signal transduction cascades that impact cell survival and axon outgrowth. In this grant application he proposes to test whether SOCS3 is essential for successful optic nerve regeneration. This will be accomplished by knocking down the expression of SOCS3 in adult retinal ganglion cells whose optic axons have been lesioned and assaying cell survival and optic axon regeneration in vivo.