The importance of transgene and cell type on the regeneration of adult retinal ganglion cell axons within reconstituted bridging grafts
| Autor: | Alan R. Harvey, Ying Hu, Qi Cui, Giles W. Plant, William T. Hendriks, Ajanthy Arulpragasam |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Retinal Ganglion Cells
Population Schwann cell Enzyme-Linked Immunosorbent Assay Ciliary neurotrophic factor Rats Sprague-Dawley Developmental Neuroscience Transduction Genetic Tubulin Neurotrophic factors medicine Glial cell line-derived neurotrophic factor Animals Ciliary Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Axon education Cells Cultured Brain-derived neurotrophic factor Analysis of Variance education.field_of_study Tissue Engineering integumentary system biology Brain-Derived Neurotrophic Factor Lentivirus Axons Rats Inbred F344 Nerve Regeneration Rats Cell biology medicine.anatomical_structure Gene Expression Regulation nervous system Neurology Retinal ganglion cell Optic Nerve Injuries biology.protein Female Schwann Cells Neuroscience |
| Zdroj: | Experimental Neurology. 207:314-328 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/j.expneurol.2007.07.001 |
| Popis: | When grafted onto the cut optic nerve, chimeric peripheral nerve (PN) sheaths reconstituted with adult Schwann cells (SCs) support the regeneration of adult rat retinal ganglion cell (RGC) axons. Regrowth can be further enhanced by using PN containing SCs transduced ex vivo with lentiviral (LV) vectors encoding a secretable form of ciliary neurotrophic factor (CNTF). To determine whether other neurotrophic factors or different cell types also enhance RGC regrowth in this bridging model, we tested the effectiveness of (1) adult SCs transduced with brain-derived neurotrophic factor (BDNF) or glial cell line-derived neurotrophic factor (GDNF), and (2) fibroblasts (FBs) genetically modified to express CNTF. SCs transduced with LV-BDNF and LV-GDNF secreted measurable and bioactive amounts of each of these proteins, but reconstituted grafts containing LV-BDNF or LV-GDNF transduced SCs did not enhance RGC survival or axonal regrowth. LV-BDNF modified grafts did, however, contain many pan-neurofilament immunolabeled axons, many of which were also immunoreactive for calcitonin gene-related peptide (CGRP) and were presumably of peripheral sensory origin. Nor-adrenergic and cholinergic axons were also seen in these grafts. There were far fewer axons in LV-GDNF engineered grafts. Reconstituted PN sheaths containing FBs that had been modified to express CNTF did not promote RGC viability or regeneration, and PN reconstituted with a mixed population of SCs and CNTF expressing FBs were less effective than SCs alone. These data show that both the type of neurotrophic factor and the cell types that express these factors are crucial elements when designing bridging substrates to promote long-distance regeneration in the injured CNS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect