Activated STAT 3 in choroidal neovascular membranes of patients with age-related macular degeneration
Elizaveta Fasler-Kan1, Kerstin Wunderlich, Pius Hildebrand
1Department of Research, University of Basel, Basel, Switzerland.
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.
Insights
STAT 3 activation is observed in retinal pigmented epithelial cells during scar formation in age-related macular degeneration (AMD) with choroidal neovascular membranes (CNVM). STAT 1 and STAT 5 were not detected in these samples.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cellular Biology
Background:
- The Janus tyrosine kinase/signal transducers and activators of transcription (Jak/STAT) pathway regulates critical cellular processes.
- Aberrant STAT protein activity, especially STAT 3 and STAT 5, is implicated in various diseases, including malignancies.
- Age-related macular degeneration (AMD) involves choroidal neovascular membranes (CNVM), a proliferative condition.
Purpose of the Study:
- To investigate the expression and activation of STAT proteins within CNVM in patients with AMD.
- To determine the role of STAT 3, STAT 1, and STAT 5 in the pathogenesis of AMD-related CNVM.
Main Methods:
- Immunohistochemical staining was employed on formalin-fixed, paraffin-embedded tissue sections from 8 AMD eyes with CNVM and 5 control eyes.
- Antibodies targeting activated STAT 1, STAT 3, STAT 5, and tenascin were used to assess protein expression.
Main Results:
- Strong positive staining for tenascin and STAT 3 was found in retinal pigmented epithelial (RPE) cells within developing scar areas of CNVM.
- STAT 3 immunoreactivity was absent in fully formed fibrovascular scar tissue.
- No STAT 1 or STAT 5 immunoreactivity was detected in any CNVM or control samples.
Conclusions:
- STAT 3 activation in RPE cells coincides with the development of scars in CNVM associated with AMD.
- STAT 1 and STAT 5 do not appear to be involved in the studied CNVM samples.
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