Survival, Regrowth, and Reconnection of Injured Retinal Ganglion Cells

Abstract

In rodents, axonal regeneration by injured retinal ganglion cells (RGCs) can follow the replacement of the optic nerve (ON) by a peripheral nerve (PN) graft that changes the nonneuronal substrate of the RGC axons and provides a link between the eye and the superior colliculus (SC). As a result of this axonal regrowth, RGCs can form well-differentiated synapses that excite or inhibit postsynaptic neurons in the SC. Because the potential source of axons to grow into the PN grafts is greatly decreased by the death of many RGCs after ON section, we compared the effects of axotomy on RGC survival and axonal transport in regenerating and axotomized RGCs. Neuronal loss was found to be greater and faster with decreasing distances between the site of axonal injury and the RGC soma. Moreover, a protracted decline in cell numbers continued for many months after axotomy. PN grafts and terminal reconnection appeared to diminish the loss of RGCs. Studies of axonal transport after ON injury revealed a selective decrease in the rate of slow transport of neurofilaments and tubulin. This change contrasts with an enhanced rate of transport of these cytoskeletal proteins when RGCs regenerated into the PN grafts. Thus, in the injured RGCs of adult rodents, the regrowth of axons and the rates of transport of cytoskeletal proteins are remarkable plastic and can be influenced by interactions among the regenerating neurons, nonneuronal components of their environment, and targets of innervation. Alterations in such interactions may be responsible for the acute and more protracted cellular events that can eventually lead to neuronal death.