Intravitreal Co-Administration of GDNF and CNTF Confers Synergistic and Long-Lasting Protection against Injury-Induced Cell Death of Retinal Ganglion Cells in Mice.
CNTF
GDNF
axotomy
lentiviral vectors
neural stem cells
neuroprotection
optic nerve
regeneration
retinal ganglion cells
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
11 09 2020
11 09 2020
Historique:
received:
09
08
2020
revised:
03
09
2020
accepted:
09
09
2020
entrez:
16
9
2020
pubmed:
17
9
2020
medline:
21
4
2021
Statut:
epublish
Résumé
We have recently demonstrated that neural stem cell-based intravitreal co-administration of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) confers profound protection to injured retinal ganglion cells (RGCs) in a mouse optic nerve crush model, resulting in the survival of ~38% RGCs two months after the nerve lesion. Here, we analyzed whether this neuroprotective effect is long-lasting and studied the impact of the pronounced RGC rescue on axonal regeneration. To this aim, we co-injected a GDNF- and a CNTF-overexpressing neural stem cell line into the vitreous cavity of adult mice one day after an optic nerve crush and determined the number of surviving RGCs 4, 6 and 8 months after the lesion. Remarkably, we found no significant decrease in the number of surviving RGCs between the successive analysis time points, indicating that the combined administration of GDNF and CNTF conferred lifelong protection to injured RGCs. While the simultaneous administration of GDNF and CNTF stimulated pronounced intraretinal axon growth when compared to retinas treated with either factor alone, numbers of regenerating axons in the distal optic nerve stumps were similar in animals co-treated with both factors and animals treated with CNTF only.
Identifiants
pubmed: 32932933
pii: cells9092082
doi: 10.3390/cells9092082
pmc: PMC7565883
pii:
doi:
Substances chimiques
Ciliary Neurotrophic Factor
0
GDNF protein, human
0
Glial Cell Line-Derived Neurotrophic Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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