Abstract
Purpose: :
STAT3 (signal transducers and activators of transcription 3) pathway has been implicated in the regulation of presumptive rod photoreceptor cells (Y. Ozawa et al. MCN: 26:258-270, 2004). In this study, we examined the consequence of constitutive activation of STAT3 in the developing eye.
Methods: :
Expression of a cDNA fragment in which residues A662 and N664 of mouse STAT3 were mutated into cystein residues was targeted to the retina under direction of an opsin promoter to generate mice with constitutive activation of STAT3 (STAT3c). Effects of STAT3 on the developing retina was investigated by Western blotting, RT-PCR, histopathology, fundoscopy, and electroretinalgram (ERG).
Results: :
Decrease in the expression of rhodopsin correlated with over-expression of STAT3. Although the eyes of the STAT3c mice appeared normal at early stages of development, we observed progressive thinning of the photoreceptor layer with ageing. The age-related changes in the retina was associated with decrease in the intensities of the A and B-waves in response to light adaption. We also observed the development of chronic inflammation in the posterior chamber with optic nerve edema, cellular infiltration, and retinal vasculitis.
Conclusions: :
Our results suggest that aberrant regulation of STAT3 pathways may promote retinal inflammation and may adversely affect the functions of photoreceptor cells by modulating rhodopsin gene expression.
Keywords: immunomodulation/immunoregulation • retinal development • signal transduction