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Ralph Hazlewood, Kathy Miller, Robert F Mullins, Markus H Kuehn, Lee M Jampol, John H Fingert; MMP19 Expression in the Human Optic Nerve. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5548.
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© ARVO (1962-2015); The Authors (2016-present)
We previously linked MMP19 mutations with a congenital malformation in which the optic disc is deeply excavated known as cavitary optic disc anomaly (CODA). The purpose of this study was to investigate the expression of MMP19, a secreted matrix metalloproteinase, within the optic nerve.
MMP19 protein expression in the optic nerve was evaluated by immunohistochemistry in sagittal and en face sections of optic nerves obtained from normal human donor eyes. Sections were co-labeled with antibodies directed against glial cells (GFAP), ganglion cell axons (βIII Tubulin), and microglia (CD45). All experiments were conducted in triplicate using three different human donor eyes.
MMP19 immunolabeling was observed throughout the optic nerve including the optic nerve head. Expression was highest in the prelaminar region and laminar region, with much lower levels in the retrolaminar region. Differential MMP19 labeling was also observed in the cross-sections of the optic nerve, with increased signal in the periphery or edges towards the scleral canal and pia mater. Additionally, no significant co-localization was observed between MMP19 and markers of glial cells, ganglion cell axons, or microglia.
Immunohistochemical analysis shows that MMP19 is strongly expressed in the optic nerve head of human donor eyes, the primary site of pathology in CODA patients. No obvious co-localization was observed with markers for cell types that populate the optic nerve, suggesting that MMP19 accumulates primarily within extracellular spaces in the optic nerve. Moreover, the lateral localization of MMP19 within the optic nerve suggests that dysregulation of its enzymatic function might undermine the adhesion between the optic nerve and the scleral canal and promote formation of an excavated optic nerve head - the key feature of CODA.
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