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J. Guo, Y.-Z. Le; Role of BCL-XL in Photoreceptor Survival Under Diabetes and Hypoxic Stress. Invest. Ophthalmol. Vis. Sci. 2009;50(13):16. doi: https://doi.org/.
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BCL-XL is an anti-apoptotic member of the BCL-2 family proteins and a cell death/survival checkpoint regulator. Our laboratory previously demonstrated that BCL-XL was a photoreceptor survival factor in rod photoreceptors under light-induced stress (IOVS, 2006 47:5583). To determine the role of BCL-XL in photoreceptor survival under diabetic and hypoxic stress and generate a mouse model of diabetes and/or hypoxia-induced photoreceptor damage, we tested the effect of BCL-XL loss in rod-specific Bcl-x knockout (KO) mice subjected to diabetic or hypoxic stress.
Streptozotocin (STZ) and cobalt chloride (CC) were used to induce diabetes or chemical hypoxia in rod photoreceptor-specific Bcl-x KO mice. Apoptosis was assessed by Western blot analysis of cell death/survival pathway-related proteins. Photoreceptor function was assessed with electroretinography (ERG). Retinal morphology was assessed by examination of H & E stained retina sections.
Loss of BCL-XL caused an up-regulation of caspase-3 and BAX in the retina of rod-specific Bcl-x KO mice subjected to hypoxia. Loss of BCL-XL caused accelerated reduction of rod photoreceptor function in diabetic rod-specific Bcl-x KO mice, which was correlated with a decrease in the thickness of photoreceptor inner nuclear layer. A detailed analysis is in progress.
Rod photoreceptor is more susceptible to diabetic stress.Therefore, BCL-XL may act as a survival factor for rod photoreceptors by suppression of caspase-related apoptotic pathway under hypoxia and diabetes.
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