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J.A. Fuller, A.M. Brun–Zinkernagel, R.S. Roque, A.F. Clark, R.J. Wordinger; Expression of p75NTR and Nerve Growth Factor in Human Optic Nerve Head and Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1247.
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Purpose: The mechanism for retinal ganglion cell (RGC) death in glaucoma is unknown. Recent studies have demonstrated that proneurotrophins are capable of elucidating apoptosis via the p75NTR neurotrophin receptor, and are a possible cause of cell death in a variety of neurodegenerative conditions. We have previously demonstrated expression and secretion of neurotrophins from astrocyte and lamina cribrosa (LC) cell cultures from the human optic nerve head. We have also demonstrated that astrocytes and LC cells are positive for the Trk A neurotrophin receptor, but are negative for p75NTR. The purpose of this study is to determine the expression patterns for p75NTR and NGF in the human retina and optic nerve. Methods:Posterior chambers from postmortem human donors were stained for p75 and NGF, as well as counterstained using neurofilament, glial fibrillary acidic protein (GFAP), as well as wheat germ agglutinin (WGA). Sections were deparaffnized, stained, and analyzed using confocal microscopy. Conditioned media was analyzed for the presence of proNGF via Western blot analysis using an antibody made against the pro segment of NGF. Results: p75NTR stains predominantly in the RGC layer of the retina, and is found in the optic nerve head, but decreases posteriorly. NGF staining is predominant in the RGC layer, and is colocalized with GFAP positive astrocytes. In addition, the 32 kDa and 53 kDa forms of proNGF were detected in LC and astrocyte conditioned medium following serum deprivation experiments. Conclusions: This study demonstrates for the first time that the RGC layer is the predominant cell layer positive for p75NTR. Furthermore, astrocytes in this layer are a potent source of NGF. Astrocyte and LC cells secrete proNGF in vitro. It is possible that NGF secreted from astrocytes in the retina and optic nerve head is in the pro form. This may induce p75NTR–mediated apoptosis of retinal ganglion cells.
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