Bcl-2 deficiency deprives peripheral nerves of neurotrophic activity against injured optic nerve.
Optic nerve injury leads to retinal ganglion cell apoptosis, thus preventing fiber regeneration. Peripheral nerve grafts are known to promote survival and regeneration in injured adult mammalian central nervous system, including optic nerve, but the mechanisms of their activity remain unclear. It is likely that they attenuate the apoptotic cascade triggered by axotomy in retinal ganglion cells. The aim of this work was to examine the role of the antiapoptotic gene bcl-2 in the optic nerve regeneration induced by such grafts. Experiments were carried out on bcl-2-deficient and wild-type mice. We have reported previously that predegeneration markedly enhances neurotrophic activity of peripheral nerve grafts, so we applied both predegenerated and non-predegenerated implants to the transected optic nerves. We studied the neurotrophic effects of bcl-2-deficient grafts on wild-type and bcl-2 knock-out optic nerves, as well as wild-type grafts on both strains of mouse optic nerves. After application of fluorescent dye to the end of the graft, we counted the stained retinal ganglion cells. Predegenerated wild-type grafts promoted survival and outgrowth of retinal ganglion cells axons in both types of mice. By contrast, non-predegenerated and predegenerated bcl-2-deficient grafts induced little or no regeneration in the optic nerves. These results indicate that the lack of bcl-2 gene does not deprive retinal ganglion cells of their regenerative potential. At the same time, we found that bcl-2 knock-out dispossesses peripheral nerves of their neurotrophic activity.
Kotulska
Katarzyna
K
Neurology Department, Medical University of Silesia, Katowice, Poland. fzjkatpl@infomed.slam.katowice.pl
Lewin-Kowalik
Joanna
J
Jaroslaw-Jerzy
Barski
B
Larysz-Brysz
Magdalena
M
Marcol
Wiesław
W
Fus
Zbigniew
Z
D000818:Animals; D002452:Cell Count; D005456:Fluorescent Dyes / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism*; D010525:Peripheral Nerves / Q000637:transplantation; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D019737:Transplants
D005456:Fluorescent Dyes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse