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B. Liu, S. Vora, A.H. Neufeld; Epidermal Growth Factor (EGF) Stimulates Formation of Tissue Specific Structures in Cultures of Optic Nerve Head (ONH) Astrocytes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3317.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have studied the cell-specific responses of astrocytes to activation of EGF receptors (EGFR) in vitro. Methods: Cell and tissue morphological appearances of human and rat ONH astrocytes, human and rat brain astrocytes and human lens epithelial cells were compared following activation of EGFR by ligand, EGF. GFAP, f-actin, tubulin, vinculin, paxcillin, fibronectin, laminin, tenascin, elastin and collagen IV were observed by immunocytochemisty. Cell proliferation was detected by BrdU labeling. AG1478 and 5-FU were tested for their abilities to block the responses to EGF. Results: By immunocytochemistry and immunoblot, EGFR was detected in human and rat astrocytes. Human and rat ONH astrocytes grown under control conditions were polygonal with short processes and formed a monolayer. Within 12 hr of treatment with EGF, ONH astrocytes were remarkably elongated with very long, thin processes. After 3 days of EGF, cells throughout the culture dish gradually reorganized to produce a cribriform appearance that had multilayers of elongated astrocytes interweaving their processes to form a network surrounding open cavities. Similar reorganization and cavity formation was observed with brain astrocytes exposed to EGF. Astrocytes attached to fibronectin after EGF treatment and reorganized to networks along fibronectin exoskeleton. BrdU labeling and 5-FU treatment demonstrated that the proliferation caused by EGF was not necessary for the reorganization. Lens epithelial cells, which have EGFR, did not demonstrate reorganization although there was significant proliferation in response to EGF. AG1478, which blocked tyrosine phosphorylation of EGFR, completely blocked the reorganization and cavity formation in response to EGF. Conclusions: EGF binding to its receptor, EGFR, causes a cell specific reorganization of astrocytes to a tissue architecture with thick cords of long slender astrocytes surrounding cell free cavities. The tissue structure that is apparent in vitro looks remarkably like the structure of the cribriform plates of the lamina cribrosa in vivo. EGF may direct the embryonic organization of astrocytes and the remodeling of the ONH in glaucomatous optic neuropathy.
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