Inactivation of Rho Increases Retinal Ganglion Cells Survival and Promotes Regeneration After Optic Nerve Axotomy

Abstract

Abstract: : Purpose: To investigate the effect of Rho GTPase inactivation on retinal ganglion cells (RGCs) survival and regeneration after optic nerve axotomy. Methods: Female Sprague–Dawley rats underwent optic nerve axotomy 1mm behind the optic disc. Animals were treated with intraocular injections of cell permeable Rho antagonists. These Rho antagonists are derivatives of C3 transferase (C. botulinum) containing a transport sequence to facilitate cell entry. Results: A single intraocular injection of Rho antagonists, applied immediately after axotomy, completely rescued RGCs examined 1 week later. Rho antagonists injected 4 days after the axotomy also resulted in a complete rescue of RGCs 1 week after the lesion. In addition to the effect on cell survival, a single intraocular injection of Rho antagonists promoted regeneration of RGC axons at 2 and 4 weeks after axotomy. Delayed treatment 4 days after lesion also promoted significant regeneration past the lesion, even though the chondroitin sulfate proteoglycans (CSPG) scar is well formed. Regeneration observed 2 weeks after axotomy was increased significantly when Rho antagonists were injected immediately after the lesion, with a repeat injection 5 and 10 days later. Conclusions: Inactivation of Rho promotes retinal ganglion cells survival and axon regeneration after optic nerve axotomy.

Keywords: ganglion cells • neuroprotection • regeneration