Retrograde Signaling in the Optic Nerve Is Necessary for Electrical Responsiveness of Retinal Ganglion Cells

PURPOSE. We investigated the role of retrograde signaling in the optic nerve on retinal ganglion cell (RGC) electrical responsiveness in the mouse model. METHODS. Electrical response of RGC was measured by pattern electroretinogram (PERG) in 43 C57BL/6J mice 4 to 6 months old under ketamine/xylazine anesthesia. PERGs were recorded before and at different times after blockade of axon transport with lidocaine at either the retrobulbar level (2 mu L, 40 mu g/mu L) or at level of the superior colliculus (SC, 1 mu L, 40 mu g/mu L). PERGs also were recorded before and at different times after optic nerve crush 1.5 mm behind the eye, followed by TUJ1-positive RGC counts of excised retinas. As controls, PERGs also were recorded after either saline injections or sham optic nerve surgery. The photopic flash electroretinogram (FERG) and visual evoked potential (FVEP) also were recorded before lidocaine and at relevant times afterwards. RESULTS. Lidocaine injection caused rapid (retrobulbar similar to 10 minutes, SC 1 hour), reversible reduction of PERG amplitude (>= 50%). Optic nerve crush caused rapid (10-20 minutes), irreversible reduction of PERG amplitude (70-75%), increase of PERG latency (>25%), as well as RGC loss (88%) 1 month after crush. FVEP was unaltered by lidocaine. For all procedures, the FERG was unaltered. CONCLUSIONS. As experimental interventions were made at postretinal level(s), PERG changes were likely associated with altered supply of retrogradely-delivered material from the SC. This implies that retrograde transport of target-derived molecules is necessary for normal RGC electrical responsiveness. The time course of early PERG changes is consistent with the speed of fast retrograde axon transport. (Invest Ophthalmol Vis Sci. 2013;54:1236-1243) DOI:10.1167/iovs.12-11188