In Vivo Evaluation of Corneal Nerves and Epithelial Healing After Treatment With Recombinant Nerve Growth Factor for Neurotrophic Keratopathy

The effect of the nerve growth factor (NGF) on chick embryo spinal ganglia was studied in the hanging-drop bioassay system by comparison with parallel development in vivo. The well-differentiated ventrolateral neuroblasts, which in vivo increase 1·33 times in size during the culture period, did not increase in size at all in vitro. Only 65–72% survived to the end of the culture period regardless of the NGF concentration. The less-differentiated mediodorsal (M-D) neuroblasts, which in vivo increase 1·31 times in size during the culture period, were found to increase equally in vitro if sufficient NGF was present. Such a quantity was greater than that which evoked maximum outgrowth of neurites. Survival of M-D neuroblasts was also related to NGF concentration but did not equal the in vivo condition even at the highest concentration. The hyperchromatic type of degeneration prevented by high NGF concentrations is that which results in vivo from insufficient peripheral field. From this and other reports it would appear that the response to NGF seen in vitro is due only to the M-D neuroblasts, and that all biochemical and cytological observations which have been reported would therefore represent conditions within those cells only.

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Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment

Scientific Reports ◽

10.1038/s41598-019-50591-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Sam W. Z. Olechnowicz ◽

Megan M. Weivoda ◽

Seint T. Lwin ◽

Szi K. Leung ◽

Sarah Gooding ◽

...

Keyword(s):

Multiple Myeloma ◽

Nerve Growth Factor ◽

Growth Factor ◽

Cell Activation ◽

Cellular Interactions ◽

Bone Microenvironment ◽

Related Factors ◽

Nerve Growth ◽

Tnf Α

Abstract Interactions between multiple myeloma (MM) and bone marrow (BM) are well documented to support tumour growth, yet the cellular mechanisms underlying pain in MM are poorly understood. We have used in vivo murine models of MM to show significant induction of nerve growth factor (NGF) by the tumour-bearing bone microenvironment, alongside other known pain-related characteristics such as spinal glial cell activation and reduced locomotion. NGF was not expressed by MM cells, yet bone stromal cells such as osteoblasts expressed and upregulated NGF when cultured with MM cells, or MM-related factors such as TNF-α. Adiponectin is a known MM-suppressive BM-derived factor, and we show that TNF-α-mediated NGF induction is suppressed by adiponectin-directed therapeutics such as AdipoRON and L-4F, as well as NF-κB signalling inhibitor BMS-345541. Our study reveals a further mechanism by which cellular interactions within the tumour-bone microenvironment contribute to disease, by promoting pain-related properties, and suggests a novel direction for analgesic development.

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