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A. Saadi, Y. Ueki, D. M. Sherry, J. D. Ash; The Signal Transducing Receptor gp130 Is Essential for Protection of Retinal Neurons From Stress-Induced Cell Death but Not for Retinal Development. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6153.
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Gp130 is the common signal-transducing receptor used by all cytokines in the interleukin-6 (IL-6) family. Activation of gp130 in retinal cells has been shown to induce various responses including: increased cell survival, inhibition of differentiation, cell fate alteration, and neuroprotection from retinal degeneration, depending on the experimental system. This study was designed to determine the role of gp130 in the developing retina in vivo.
Retina specific gp130 conditional knockout mice were made by crossing gp130flox/flox mice to Chx10-Cre mice. Retinas from the resulting Chx10-Cre+/-;gp130flox/flox (Cre+) and Chx10-Cre-/-;gp130flox/flox (Cre-) mice were used for histological and ERG analyses. Cre+ and Cre- retinas from different developmental postnatal days: P0, P4, P6, P8, P10, P12, P14, and P30 were used for Western blot, real-time PCR, and immunohistochemical analysis with different retinal cell type markers. To determine the neuroprotective effect of gp130-mediated signaling on photoreceptor survival, six-week old Cre+ and Cre- mice were exposed to continuous 1000 lux fluorescent light for 0 to 4 days after which ERG and histological analyses were performed.
PCR, real-time PCR, and western blot analysis showed an 80% reduction in gp130 mRNA and protein in retinas from Cre+ mice compared to Cre- controls. Retinal morphology, cell differentiation, cell fate, synaptic organization, and ERG in gp130 deficient retina were all similar to wild-type retina. However, when the mice were oxidatively stressed by exposure to constant bright light, gp130 deficient mice had greater sensitivity to light damage relative to wild-type controls.
gp130 does not play an essential role in regulating developmental timing or cell fate decisions in normal retinas as previously suggested; rather our data clearly demonstrate that gp130 is essential for neuroprotection from oxidative damage.
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