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L. Zheng, R.E. Anderson, M.–P. Agbaga, E.B. Rucker, III, Y.–Z. Le; Loss of Bcl–XL Causes Increased Rod Photoreceptor Susceptibility to Bright Light Damage . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2044.
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© ARVO (1962-2015); The Authors (2016-present)
During our study of bright light–induced protein expression, BCL–XL, an anti–apoptotic member of BCL–2 family proteins and a cell death/survival checkpoint regulator, was shown to be up–regulated in bright light damaged mouse photoreceptors. To investigate the significance of BCL–XL up–regulation in the bright light damage model, we disrupted Bcl–x gene specifically in mouse rod photoreceptors and characterized the effect on retinal apoptosis, function, and morphology.
Rod–specific Bcl–x knockout mice were generated by mating mouse opsin promoter controlled Cre mice with floxed Bcl–x mice, both of which were on an albino background. Loss of BCL–XL in the retina was confirmed by Western blots and immunohistochemistry. At 6–8 weeks of age, offspring were placed under constant bright light stress. Retinal apoptosis was characterized with TUNEL assay and DNA fragmentation assay. Photoreceptor structural and functional integrity was measured by quantitative morphometry (outer nuclear layer (ONL) thickness) and electroretinography (ERG).
Disruption of Bcl–x specifically in rods caused decreased BCL–XL expression, increased DNA fragmentation and apoptosis, decreased scotopic ERG amplitudes, and decreased ONL thickness in bright light exposed mice.
Our study demonstrates that loss of BCL–XL increases rod photoreceptor susceptibility to bright light damage. Although the biochemical mechanism(s) of BCL–XL in photoreceptor death/survival is virtually uninvestigated, our results suggest that BCL–XL, a widely regarded upstream regulator of caspase–dependent apoptotic pathways, is involved in photoreceptor survival under light damage conditions.
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