Activated STAT3 in Choroidal Neovascular Membranes of Patients with Age-Related Macular Degeneration

PURPOSE: The Jak/STAT (Janus tyrosine kinase/signal transducers and activators of transcription) pathway is critical for growth control, developmental regulation and homeostasis. Here we studied the expression of STAT proteins in the proliferative disease of age-related macular degeneration (AMD) with choroidal neovascular membranes (CNVM). The STAT family are of cytoplasmic proteins with roles as signal messengers and transcription factors that participate in normal cellular responses to cytokines and growth factors. Abnormal activity of certain STAT family members, particularly STAT 3 and STAT 5, is associated with a wide variety of human malignancies and other diseases. Here were studied STAT activation in CNVM of patients with AMD. METHODS: Sections of formalin-fixed, paraffin-embedded samples from 8 eyes with AMD and 5 controls were included in this study. Immunohistochemical staining was performed using antibodies against activated STAT 1, STAT 3 and STAT 5 proteins, and tenascin. RESULTS: In CNVM, we observed a strong positive staining for tenascin and STAT 3 in retinal pigmented epithelial (RPE) cells restricted to areas of developing scars. In contrast, STAT 3 immunoreactivity failed in areas completely composed of fibrovascular disciform scar material. In addition, no immunoreactivity for both STAT 1 and STAT 5 was detected in all CNVM and in all control samples. CONCLUSION: In CNVM, activation of STAT 3 appears in RPE cells simultaneously with the formation of scars.