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Editors Selection IGR 12-1
Basic Science: Neuroprotection
Comment by Jeffrey Goldberg on:
59230 Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice, Flachsbarth K; Kruszewski K; Jung G et al., Investigative Ophthalmology and Visual Science, 2014; 55: 7029-7039
In this article, Flachsbarth and colleagues report on experiments in which they used neural stem cells transduced to express ciliary neurotrophic factor (CNTF) as a delivery vehicle to look for retinal ganglion cell (RGC) neuroprotection and regeneration after optic nerve crush injury. Compared to injected control neural stem cells not expressing CNTF, those expressing CNTF showed significantly higher levels of RGC survival and optic nerve axon regeneration up to four months after injury. Of note, loss of RGCs appears to have been stabilized by three months after injury, suggesting a long term halt to RGC loss may be possible. Comparison between control cells and no cells would have been interesting, as various stem cell populations have previously been demonstrated to produce considerable levels of neurotrophic factors without transduction of additional genes. It was also interesting to note the relatively weak regenerative response at four months, with few axons traveling long distances.
An important question for the future might be to directly explore bolus versus sustained delivery, and sustained delivery by viral vectors versus by cell transplant
CNTF has a long history in the preclinical literature of promoting survival and regeneration of RGCs in various models of optic nerve injury from mice to monkeys. Delivery has ranged from bolus injections, repeat bolus injections, to viral transduction of retinal cells. How does the current paper compare to other CNTF delivery experiments? Perhaps comparison to the human experimental use of encapsulated cell technology in Neurotech's NT501 device is worth considering. The NT501 device secretes approximately 20 ng/day. In this paper, CNTF secretion in culture was estimated at approximately 90 ng/10^5 cells/day in these experiments. An important question for the future might be to directly explore bolus versus sustained delivery, and sustained delivery by viral vectors versus by cell transplant.
Overall, this paper adds to an already considerable body of literature on the use of this neurotrophic factor to promote RGC survival and regeneration, and further supports the premise of translating this promising candidate towards possible human use.
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