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Z. Hao, C. Guo, S. Dufour, X. Jiang, R. Cone, D.-N. Hu, N. Charkraborty, J. O'Rourke; Neural Crest-Derived Tissue Plasminogen Activator Within the Mammalian Eye:Anatomic Distribution Revealed by a New Transgenic Marker. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4368.
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Long thin sympathetic axons transport tissue plasminogen activator(t-PA) to the eye. There it is released in response to adrenergic stimulations. The t-PA is synthesized and packaged in transport vesicles in superior cervical sympathetic ganglion neuron cell bodies(1) .Plasmin activated by t-PA has long been thought to accelerate the trabecular outflow of aqueous humor. Our purpose here is to map the neural crest origins of cells able to produce t-PA within the eye.
A promoter mouse line- whose human t-PA Cre transgene is specifically expressed by sympathetic nerves and all other crest derivatives(2)- was crossed with a Lac Z reporter expressing the enhanced green fluorescent protein(EGFP) transgene. PCR sorted pups showed both t-PA promoter and EGFP expressions confined within crest-derived cells. Cryosections were viewed by confocal and UV microscopy ,and immunostained for t-PA antigen.Cultured human uveal melanocytes were stimlated with phenylephrine to confirm a t-PA enzyme release; and immunostained to reveal cell membrane alpha 1 adrenergic receptors.
Bright discreet promoter expressions ,to be shown ,appeared in fine (0.5-2.0 micron wide) crest- derived uveal and corneal nerve filaments;corneal and trabecular endothelium; uveal melanocytes;and unexpectedly in retinal ganglion,bipolar and, photoreceptor cells(see figure below), the optic nerve and chiasm. Cultured melanocyte t-PA basal release increased 70-80% following alpha 1 receptor stimulations.
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