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WS Lambert, RJ Wordinger, AF Clark; Expression of Neuroprotective Factors by Cultured Cells of the Human Optic Nerve Head Following In Vitro Ischemia . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2183.
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Purpose: There is evidence that ischemia within the optic nerve head (ONH) contributes to neuronal loss in primary open angle glaucoma (POAG), an optic neuropathy characterized by retinal ganglion cell (RGC) death and visual field loss. The expression of "neuroprotective factors", such as neurotrophins (NTs) and transforming growth factor-beta (TGFb), by neurons and glia has been shown to increase following ischemia. The expression of NTs and TGFbs have been demonstrated within the ONH (Lambert et al. 2001 IOVS 42:2315-2323, Pena et al. 1999 Br J Ophthal 83:209-218). The purpose of this study was to determine if cells from the human ONH upregulate the expression of neuroprotective factors following in vitro ischemia. Methods: Lamina cribrosa (LC) and ONH astrocytes were cultured under the following conditions for 48 hours: in vitro ischemia (glucose free/serum free media, 95% N2/5% CO2), in vitro ischemia followed by a 24 hour recovery period (growth media plus serum, 95% air/5%CO2), or normal conditions (growth media plus serum, 95% air/5%CO2). Total cellular protein was extracted and subjected to SDS-PAGE followed by Western blotting. Conditioned media was collected and the secretion of neuroprotective factors was examined using immunoassays. Results: In general the expression of NTs, trk receptors, TGFb isoforms and TGFb receptors was decreased in LC cells and ONH astrocytes following in vitro ischemia. An increase in expression was observed for the following proteins: NGF (58 kDa isoform), BDNF (78 kDa), NT-3 (78 kDa) and TGFb-3 (65 kDa). There appeared to be no change in the expression of Trk A following in vitro ischemia. TGFb-1 and TGFb-2 secretion by LC cells and ONH astrocytes, and BDNF secretion by ONH astrocytes was decreased following in vitro ischemia. The secretion of NGF by both cell types, and BDNF by LC cells was increased by in vitro ischemia. The secretion of NT-3 or NT-4 by either cell type was not detected under any condition. Conclusion: Cultured cells from the optic nerve head respond to ischemic conditions by altering the expression of neuroprotective factors and their receptors. An increase in NGF and BDNF protein and secretion was detected following ischemia, suggesting that LC cells and ONH astrocytes may be capable of expressing neuroprotective factors for RGCs in POAG. A better understanding of NT and TGFb signaling within the ONH could result in the development of new therapies for POAG.
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