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JK Klarlund, D Olejniczak; Enhanced Outgrowth of Neurites in Response to Phosphatidic Acid . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1617.
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Purpose:Innervation is crucial for normal function of the cornea. Loss of proper sensory innervation compromises healing in response to injury and may result in neurotropic ulceration. Therefore, there is great interest in identifying factors that promote growth of nerve fibers. We have examined the role of phospholipase D 2 (PLD2) and its reaction product, phosphatidic acid in neurite extension. Methods:The PC12 cell line is commonly used as a model for molecular mechanisms that determine extension of neurites in the peripheral nervous system. Results:Transfection of PLD2, which is constitutively active, into PC12 cells resulted in extension of neurites. No effect was seen with a catalytically inactive mutant of PLD2 or with phospholipase D1. Treatment of PC12 cells with nerve growth factor leads to development of neurites, and a very significant synergistic effect was observed in cells co-transfected with PLD2. Interestingly, addition of phophatidic acid directly to the tissue culture media resulted in neurite extension, and a synergistic effect was seen with nerve growth factor. Several other lipids were found to be inactive. Conclusion:These results indicate that phosphatidic acid enhances extension of neurites. Phosphatidic acid is therefore a potential target for development of drugs to enhance corneal innervation
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