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Y. Ueki, Y. Z. Le, J. D. Ash; Activation of the Signal-Transducing Receptor gp130 in Photoreceptors Is Essential for Endogenous Protection From Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):696.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that exposure of animals to sub-lethal levels of bright cyclic light (preconditioning) and inherited mutations induce a stress response in photoreceptors. We and others have shown that the stress response can protect photoreceptors from a subsequent damaging insult. We predict that the induced protective mechanism may also delay inherited retinal degeneration. The objective of this study was to determine whether or not gp130 is essential for stress-induced endogenous photoreceptor protection.
Rod photoreceptor-specific gp130 knockout mice were generated by using the Cre/lox system. Endogenous protection was induced in mice by exposure to 600 lux cyclic light for 6 days (preconditioning). At the end of preconditioning, mice were then evaluated for protection from retinal degeneration caused by light damage. We also crossed our rod photoreceptor-specific gp130 knockout mice with transgenic mice expressing a mutant from of opsin (VPP) to determine if loss of gp130 accelerated retinal degeneration. The rate of photoreceptor degeneration was measured by electroretinography (ERG) and histology.
Our conditional gp130 mice show a loss of gp130 activity in approximately 30-40% of photoreceptors, without affecting other cell types. Our ERG and histological data clearly show that preconditioning induces endogenous protection from light damage, and that loss of gp130 in rod photoreceptors impairs preconditioning-induced protection. In our genetic model of photoreceptor degeneration, loss of gp130 in rod photoreceptors accelerated the rate of photoreceptor cell death in VPP mice.
Our data show that the absence of gp130 in photoreceptors impairs stress-induced endogenous protection and increases sensitivity to both light- and genetically-induced photoreceptor cell death. This study provides direct evidence that gp130 activity in photoreceptors is essential for endogenous protection of photoreceptors from chronic stress.
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