The Distribution of SPARC in Surgically Excised Choroidal Neovascular Membranes Associated With Age-Related Macular Degeneration

Abstract

Abstract: : Purpose: SPARC is a matricellular protein that is thought to be involved both in angiogenesis and wound repair. The aim of this study was to investigate the expression and distribution of SPARC in human choroidal neovascularization (CNV) associated with age-related macular degeneration. Methods: CNV membranes were surgically removed from 6 patients with age-related macular degeneration. All membranes were fixed in formalin, embedded in wax and serially sectioned for histochemical and immunohistochemical evaluation. Immunoreactivity for monoclonal antibodies against SPARC was compared to that for cell markers specific for endothelial cells (von Willebrand factor), differentiated RPE (pan cytokeratins), dedifferentiated RPE (RGE53) and macrophages (CD68). Results: All CNV membranes were positive for SPARC, which was localized to cells populating the extracellular matrix stroma. Dedifferentiated, fibroblastic RPE cells appeared throughout the stroma of CNV membranes and showed intense SPARC positivity. Feint, diffuse immunoreactivity for SPARC was also found in areas of intact, differentiated RPE monolayer. Endothelial cells in highly vascularized areas of CNV membranes, as well as CD68-positive were also positive for SPARC, presenting similar, intermediate levels of staining. Conclusions: Our results support the hypothesis that SPARC has a role in the cellular pathogenesis of CNV in humans. The heterogeneous levels of staining intensity may provide insights to specific cellular sites of expression. Understanding the cellular mechanisms of CNV formation may provide novel rationales for the development of new pharmacological therapies for CNV.

Keywords: choroid: neovascularization • age-related macular degeneration • extracellular matrix