Bone marrow mononuclear cells increase retinal ganglion cell survival and axon regeneration in the adult rat.
The central nervous system (CNS) of adult mammals generally does not regenerate, and many studies have attempted to identify factors that could increase neuroprotection and/or axonal outgrowth after CNS lesions. Using the optic nerve crush of rats as a model for CNS injury, we investigated the effect of intravitreal transplantation of syngeneic bone-marrow mononuclear cells (BMMCs) on the survival of retinal ganglion cells (RGC) and on the regeneration of optic axons. Control animals received intravitreal saline injections after lesion. Injections of BMMCs resulted in a 1.6-fold increase in the number of RGCs surviving 14 days after injury. The BMMC-treated animals also had increased numbers of axons, which grew up to 1.5 mm from the crush site, and also had reduced Müller glia activation. Analysis of mRNAs in all conditions revealed an increase in levels of fibroblast growth factor 2 (FGF-2) mRNA in treated animals 14 days after injury. To investigate whether the regenerated axons could reach the brain, we retrograde labeled the RGCs by injecting a lipophilic tracer into the superior colliculus. We also analyzed the expression of NGFI-A in the superficial layers of the superior colliculus as a possible marker of synaptic input from RGC axons. We found evidence that more RGCs were able to reach the brain after treatment and we showed that NGFI-A expression was higher in the treated animals 60 days after injury. These results demonstrate that transplant of BMMCs can increase neuroprotection and neuroregeneration after injury in a model of optic nerve crush, and these effects could be mediated by FGF-2.
Zaverucha-do-Valle
Camila
C
Programa de Terapia Celular and Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Gubert
Fernanda
F
Bargas-Rega
Michelle
M
Coronel
Juliana L L
JL
Mesentier-Louro
Louise A
LA
Mencalha
Andre
A
Abdelhay
Eliana
E
Santiago
Marcelo F
MF
Mendez-Otero
Rosalia
R
D000818:Animals; D001369:Axons / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology*; D013477:Superior Colliculi / Q000378:metabolism
C490623:Nab1 protein, rat; D012097:Repressor Proteins; D016222:Fibroblast Growth Factor 2