Bcl-2 overexpression per se does not promote regeneration of neonatal crushed optic fibers.
We have explored whether overexpression of the bcl-2 gene 'per se' can promote regeneration of retinal ganglion cells (RGCs) after optic nerve axotomy in developing transgenic mice. We have used newborn mice (postnatal day 5) because at this age the central nervous system environment is more permissive for regeneration than in adults, thus, maximizing the probability to detect a regeneration-promoting role of bcl-2. Thirty days postsurgery we found that in mice overexpressing bcl-2, a high proportion of retinal ganglion cells survived and also that some fibers in the proximal stump of the optic nerve were preserved. However, the optic nerve of transgenic mice does not show signs of regeneration. On the contrary, in the presence of Schwann cell transplants, there are signs of fiber regrowth. Indeed, many axonal terminals cross the crush site and reach the chiasm in both wild type and transgenic mice nerves. These results suggest that bcl-2 overexpression is not sufficient 'per se' to increase the regenerative potentiality of axotomized RGCs.
Lodovichi
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C
Istituto di Neurofisiologia del CNR, Area di Ricerca CNR, Via Alfieri 1, 56100 Pisa, Italy.
Di Cristo
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G
Cenni
M C
MC
Maffei
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L
D000818:Animals; D000831:Animals, Newborn; D005136:Eye Proteins / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009897:Optic Chiasm / Q000473:pathology; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000503:physiopathology* / Q000628:therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation
D005136:Eye Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins