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STAT3-Mediated Signaling in the Determination of Rod Photoreceptor Cell Fate in Mouse Retina

¹From the Departments of Pathology, ²Ophthalmology, ³Internal Medicine, and ⁴Neurobiology, Yale University School of Medicine, New Haven, Connecticut.

PURPOSE. The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the development of rod photoreceptors in the mouse retina.

METHODS. Retina explant cultures derived from timed-pregnant CD-1 mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted retinas were harvested at distinct time points and processed for immunohistochemistry.

RESULTS. Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal development of rods in retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod development by CNTF.

CONCLUSIONS. These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development.

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