title: Axonal regeneration of retinal ganglion cells after optic nerve pre-lesions and attachment of normal or pre-degenerated peripheral nerve grafts.
abstract: Axonal regeneration of retinal ganglion cells (RGCs) into a normal or pre-degenerated peripheral nerve graft after an optic nerve pre-lesion was investigated. A pre-lesion performed 1-2 weeks before a second lesion has been shown to enhance axonal regeneration in peripheral nerves (PN) but not in optic nerves (ON) in mammals. The lack of such a beneficial pre-lesion effect may be due to the long delay (1-6 weeks) between the two lesions since RGCs and their axons degenerate rapidly 1-2 weeks following axotomy in adult rodents. The present study examined the effects of the proximal and distal ON pre-lesions with a shortened delay (0-8 days) on axonal regeneration of RGCs through a normal or pre-degenerated PN graft. The ON of adult hamsters was transected intraorbitally at 2 mm (proximal lesion) or intracranially at 7 mm (distal lesion) from the optic disc. The pre-lesioned ON was re-transected at 0.5 mm from the disc after 0, 1, 2, 4, or 8 days and a normal or a pre-degenerated PN graft was attached onto the ocular stump. The number of RGCs regenerating their injured axons into the PN graft was estimated by retrograde labeling with FluoroGold 4 weeks after grafting. The number of regenerating RGCs decreased significantly when the delay-time increased in animals with both the ON pre-lesions (proximal or distal) compared to control animals without an ON pre-lesion. The proximal ON pre-lesion significantly reduced the number of regenerating RGCs after a delay of 8 days in comparison with the distal lesion. However, this adverse effect can be overcome, to some degree, by a pre-degenerated PN graft applied 2, 4, or 8 days after the distal ON pre-lesion enhanced more RGCs to regenerate than the normal PN graft. Thus, in order to obtain the highest number of regenerating RGCs, a pre-degenerated PN should be grafted immediately after an ON lesion.
authors.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong, China.
authors.forename: Si-Wei
authors.initials: SW
authors.lastname: You
authors.forename: Kuldip S
authors.initials: KS
authors.lastname: Bedi
authors.forename: Henry K
authors.initials: HK
authors.lastname: Yip
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D006224:Cricetinae; D005260:Female; D008647:Mesocricetus; D009410:Nerve Degeneration / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000503:physiopathology* / Q000637:transplantation*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D013997:Time Factors