Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury.
BACKGROUND
We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals.


RESULTS
As previously reported we found that the Wld(S) mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that Wld(S) transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in Wld(S) and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in Wld(S) transgenic rats.


CONCLUSIONS
RGC axon regeneration is similar between Wld(S) transgenic and wildtype rats, but Wld(S) transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the Wld(S) protein.
Centre for Brain Repair, University of Cambridge, UK.
Barbara
B
Lorber
Alessia
A
Tassoni
Natalie D
ND
Bull
Marilita M
MM
Moschos
Keith R
KR
Martin
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D007905:Lens Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009901:Optic Nerve Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D055647:Rats, Transgenic; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C533642:Wld protein, rat; C063843:insulin gene enhancer binding protein Isl-1