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R. Agarwal, L. Jackson, X. Liu, A.F. Clark, R.J. Wordinger; Cells Isolated from the Human Optic Nerve Head Expresses Components of the Notch Signaling Pathway . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3340.
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Purpose: The Notch signaling pathway mediates cell-cell interactions including the maintenance of cellular differentiation in highly organized tissues. Notch is a single pass transmembrane receptor activated by membrane bound ligands located on neighboring cells. Four Notch isoforms (Notch-1, -2, -3, -4) and 2 ligands (Jagged-1; Jagged-2) have been reported in the mammalian pathway. Upon ligand binding to Notch, presenilin and nicastrin are known to be involved in the enzymatic cleavage of the Notch receptor to yield the Notch intracellular component (NIC) that translocates to the nucleus and activates gene expression. The human optic nerve head (ONH) is a highly organized tissue that contains numerous cells in close approximation. In glaucoma the ONH is altered and cell-cell communication may play a role in the pathophysiology of the disease. The purpose of this study is to determine if cells isolated from the human optic nerve head express components of the Notch signaling pathway. Methods: Well-characterized human lamina cribrosa (N=6) and ONH astrocyte (N=4) cell lines were utilized. The expression of mRNA for Notch 1-4, Jagged-1 Jagged-2, and presenilin was examined by RT-PCR. Protein expression for the same components was examined using immunohistochemistry and Western blotting. Results: Using RT-PCR, mRNA for Notch 1-3, Jagged-1, Jagged-2, and presenilin was detected in both lamina cribrosa and ONH astrocytes. mRNA for Notch-4 was not detected in any cell line. The presence of protein for Notch 1-3, Jagged-1, Jagged-2, and presenilin was demonstrated in both lamina cribrosa cells and ONH astrocytes via immunohistochemistry. Western blots were also positive for Jagged-1 and Jagged-2. Conclusions: These studies demonstrate for the first time that cells isolated from the human ONH express components of the Notch signaling pathway. This raises the possibility that cell-cell signaling via Notch may occur in the human ONH. CR: F, E. Support: NIH Grant EY12783 and Alcon Research Ltd., Fort Worth, TX.
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