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G. Malek, K. Wu, A. D. Proia, S. Cousins; Expression Pattern of Osteopontin and Macrophages in Neovascular Age-Related Macular Degeneration and Experimental Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1163.
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Osteopontin (OPN) is a non-collagenous, extracellular matrix sialoprotein implicated in inflammation, cell migration, and tissue remodeling, processes important in the pathobiology of neovascular age-related macular degeneration (NVAMD). It has chemotactic activity for smooth muscle cells, and may be a possible macrophage chemotactic and retention factor in systemic and neurologic diseases including atherosclerosis and Alzheimer’s disease. Immunohistochemical studies of NVAMD have localized macrophages and smooth muscle actin positive cells to excised NV lesions. We investigated the expression of OPN and its integrin receptors in human NVAMD and mouse eyes with experimental choroidal neovascularization (CNV).
We evaluated cryo- and paraffin sections of whole post mortem human eyes with NVAMD and age-matched normals or eyes with drusen. We also evaluated cryosections from mice at different time points after induction of experimental laser CNV. All samples were probed with antibodies to OPN and integrin receptors vβ1, vβ3, vβ5 and CD45 as well as cellular markers including GFAP, Vimentin (müller cells), F4-80 (murine macrophages), Iba-1, CD68 (microglia and macrophages), smooth muscle actin (mesenchymal cells).
In retinas from normal donors, OPN localized to the optic nerve and nerve fiber layer, but not in the choroid or elsewhere in the retina. In eyes with either drusen or NVAMD, OPN upregulation was observed in the inner and outer plexiform layer (presumably associated with Muller cell processes), and surrounding retinal vessels. Muller cell activation was observed in regions overlying CNV in both human and mouse eyes. In human retinas overlying drusen, CNV and murine CNV, extensive macrophage/microglia infiltration was observed throughout the retina not apparent in normals. Within the CNV itself, macrophages were abundant within most human and murine specimens. In murine experimental CNV, OPN immunoreactivity was evident within early CNV lesions at times when macrophage infiltration is significant. However, OPN was absent from late stage fibrotic CNV lesions.
To our knowledge this is the first report of retinal expression of OPN and the presence of macrophages in the neurosensory retina overlying drusen and NVAMD. Localization of OPN and macrophages in plexiform layers of AMD eyes suggests that OPN may be a recruitment and retention factor for macrophages, possibly contributing to synaptic remodeling and retraction previously observed in retina overlying drusen and CNV in human AMD.
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