Background: Retinal pigment epithelial cells constitute an important component of the
blood–retinal barrier and play a pivotal role in the development of age-related macular
degeneration (AMD). Understanding the underlying molecular mechanisms is a prerequisite
for developing therapeutic strategies for the treatment of this disease. This study investigated
cytokine-induced changes of the JAK–STAT (Janus tyrosine kinase–signal transducers and
activators of transcription) signaling pathway in the human retinal pigment epithelial cell line
ARPE-19 and potential implications for AMD.
Methods: Electromobility shift assay, immunofluorescence staining, and flow cytometry were
used to evaluate the JAK–STAT pathway in the ARPE-19 cell line.
Results: We examined cytokine-induced expression of STATs in the ARPE-19 cell line. Strong
STAT1 activation determined by electromobility shift assay and flow cytometry was demonstrated
upon exposure to interferon-γ. Interferon-α upregulated STAT1, STAT2, and STAT3 in
ARPE-19 cells, while interleukin-6 (IL-6) and IL-4 activated STAT3 and STAT6, respectively.
Confocal microscopy identified the nuclear translocation of the STAT proteins. Flow cytometry
analysis demonstrated the upregulation of major histocompatibility complex molecules on
ARPE-19 cells as responses to interferon-α and interferon-γ.
Conclusion: Our data demonstrate the upregulation of members of the JAK–STAT signaling
pathway in the ARPE-19 cells upon stimulation with interferon-α, interferon-γ, IL-4, and IL-6.
We present a model for these signaling pathways potentially relevant for AMD, which may
prove useful for screening of AMD therapeutics.