Development of new method for optic nerve regeneration-a combined approach of the peripheral nerve transplant and intraocular injection of neurotrophins.

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In mammals, retinal ganglion cells can not regenerate their axons after axotomy and their somas suffer from retrograde cell death. With peripheral nerve graft, however, axons of retinal ganglion cells can regrow through the grafted nerve. So far the number of regrowing axons is reported to be less than 5% of the total optic nerve fibers. To enhance cell servival and axonal regeneration of axotomized retinal ganglion cells, we tried to examine the effects of intraocular injections of various neurotrophins on cell survival and axonal regeneration in combination with the peripheral nerve graft. We made the following findings : (1) Intraocular injection of brain derived neurotrophic factor (BDNF) promotes axonal regrowth of retinal ganglion cells withih the retina but it is not effective for these intraretinal axons to penetrate into the optic nerve, suggesting existence of some non-permissive molecules around the optic disc. (2) Thus, the intraocular injections of BDNF in combination with the peripheral nerve graft was not effective to improve the number of ganglion cells with regenerated axons into the graft. (3) Low affinity NGF receptor (LNGFR) and some neurotophin receptor mRNAs were localized in subpopulations of retinal ganglion cells. (4) The surviving retinal ganglion cells without regenerating axons could be distinguished from those with regenerated axons by immunostaining with the monoclonal antibody C38 that we have recently isolated.