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C. Lange, M. Thiersch, M. Samardzija, C. Grimm; The Differential Role of JAK-STAT Signaling in Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4486.
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We recently showed that Jak2, STAT1 and STAT3 are involved in photoreceptor apoptosis in the model of light-induced retinal degeneration. Here we studied retinal expression of various other members of the Jak-STAT signaling pathway after light exposure and in inherited models for retinal degeneration (RD).
For the induced model balb/c mice were exposed to light (5 klux) for 1 hour. Retinas were isolated at different time points after light exposure. Rd1 and VPP mice served as inherited models. Retinas were taken at different time points after birth. Gene expression was determined by semi-quantitative real time polymerase chain reaction (real time PCR).
We show that expression of Jak3 was similarly induced in the retina of light exposed, rd1 and VPP mice. In contrast, the mRNAs of STAT1-STAT3 and Src-homology 2 domain phosphatase-1 (shp-1) were induced strongly after light exposure, slightly in VPP mice but not in rd1.
Since the presence of a stimulus toxic to the retina (light, gene mutation) induced the expression of Jak3, Jak3 might be part of an endogenous response to retinal stress. The induction of Jak3 after injection of Leukemia inhibitory factor (LIF) and the absence of Jak3 induction in LIF-/- after light suggest that Jak3 might be part of the neuroprotective response mediated by LIF. Shp-1 was selectively induced in retinas of animals undergoing light-induced photoreceptor apoptosis and slightly in the VPP mouse model. Expression of shp-1 correlated with the level of Jak2 phosphorylation. This suggests a direct or indirect interaction between these proteins to regulate a Jak2 dependent response. The lack of shp-1 induction and Jak2 phosphorylation in the rd1 retina further supports the conclusion that the molecular mechanisms of photoreceptor cell death strongly depend on the nature of the apoptotic stimulus.
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