Ciliary neurotrophic factor promotes the regrowth capacity but not the survival of intraorbitally axotomized retinal ganglion cells in adult hamsters

Abstract

Ciliary neurotrophic factor has recently been shown to promote the axonal regrowth of retinal ganglion cells into a peripheral nerve graft following an intracranial transection of the optic nerve (~7mm from the optic disc). It is unclear whether the enhancement of axonal regrowth by ciliary neurotrophic factor application correlates with the enhancement of survival of retinal ganglion cells and/or the up-regulation of expression of growth-associated protein-43 messenger RNA in retinas. The present study evaluated the regenerative capacity of retinal ganglion cells following intraorbital transection of the optic nerve (~1.5mm from the optic disc) and the attachment of a peripheral nerve to the ocular stump of the optic nerve. In addition, we have determined the survival of retinal ganglion cells and the expression of growth-associated protein-43 messenger RNA in ciliary neurotrophic factor-treated retinas following optic nerve transection. The results showed that in the ciliary neurotrophic factor-treated retinas, the number of retinal ganglion cells which had regrown axons into a peripheral nerve is about four times more than the control. In the axotomized retinas, ciliary neurotrophic factor initiated sprouting of axon-like processes at 14 and 28 days post-axotomy and up-regulated the expression level of growth-associated protein-43 messenger RNA at 7,14 and 28 days post-axotomy. However, ciliary neurotrophic factor did not prevent the death of axotomized retinal ganglion cells.We suggest that one possible mechanism for the axonal regeneration of axotomized retinal ganglion cells by ciliary neurotrophic factor could be mediated by the up-regulation of growth-associated protein-43 gene expression and not by increasing the pool of surviving retinal ganglion cells after axotomy. Copyright (C) 1999 IBRO.