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 STATs are 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 STAT3 and STAT5, 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 STAT1, STAT3 and STAT5 proteins, and tenascin. Results: In CNVM, we observed a strong positive staining for tenascin and STAT3 in retinal pigmented epithelial (RPE) cells restricted to areas of developing scars. In contrast, STAT3 immunoreactivity failed in areas completely composed of fibrovascular disciform scar material. In addition, no immunoreactivity for both STAT1 and STAT5 was detected in all CNVM and in all control samples. Conclusion: In CNVM, activation of STAT3 appears in RPE cells simultaneously with the formation of scars.

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