Abstract
Purpose: :
Age–related macular degeneration (ARMD) is the leading cause of blindness in industrialized countries. In certain cases, ARMD can progress to a state of advanced choroidal neovascularization (CNV) with devastating effects on central vision. Treatment of CNV includes thermal laser photocoagulation and surgical excision of the choroidal membranes but these options have limited success. Prostate–specific membrane antigen (PSMA) is a type II transmembrane glycoprotein expressed predominantly in prostatic tissue. PSMA is also expressed in tumor–associated neovessels of several solid tumors such as colorectal and renal cell carcinoma. Although the significance of PSMA expression in tumor–associated endothelium is unknown, its location on endothelial cells represents a potential target for antiangiogenic therapy. To the best of our knowledge, PSMA expression in a non–neoplastic setting, such as CNV, has never been described. The purpose of this study was to evaluate the immunohistochemical expression of PSMA in CNV.
Methods: :
Twenty–nine surgically excised choroidal neovascular lesions obtained from ARMD patients were formalin–fixed, paraffin–embedded, and five micron sections were cut. Immunohistochemistry was performed using a standard Avidin–Biotin Complex method for each antibody. Monoclonal antibody for factor VIII (Dako) and monoclonal anti–PSMA antibody (NCL–L–PSMA, Novocastra, NewCastle, United Kingdom) were used for all cases. Normal choroidal and retinal vessels were used as positive controls for factor VIII. Human hyperplastic prostate tissue was used as positive control for PSMA.
Results: :
Immunohistochemical staining revealed that all twenty–nine samples were positive for factor VIII in the endothelial surface of the neovascular membranes. Double staining with PSMA was performed and the positive factor VIII endothelial cells were consistently negative for PSMA. The vascular wall, which was evaluated in all specimens, was negative for both antibodies. The staining did not vary depending on the number, size of the wall or caliber of the neovessels in all twenty–nine neovascular membranes.
Conclusions: :
Choroidal neovascular membranes are positive for immuno markers of endothelial cells. The absence of PSMA in chroidal neovascular membranes supports the hypothesis that PSMA is only expressed in prostate and tumor–associated neovascularization. In addition, this negative result regarding PSMA is important to report in order to eliminate PSMA as a potential target for the treatment of ARMD.
Keywords: age-related macular degeneration • neovascularization • immunohistochemistry