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M. Doly, O. Perche, C. Cercy, I. Ranchon-Cole; Caspase-12 Play a Role in Light-Induced Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4485.
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To study caspase-12 in light-induced retinal degeneration
Wistar rats were raised in dim-cyclic light. In a first set of experiments, rats were uninjected or injected with DMSO 2% or the caspase-12 inhibitor Z-ATAD-FMK (0,4 mM). They were placed in the dark before being exposed for 24 hours to 2700 or 3400 lux-light. They were sacrificed at 0, 2 or 24 hours of light-exposure to measure caspase-12 activity in the retina. In a second set of experiments, rats were uninjected or injected with DMSO 2% or Z-ATAD-FMK before being exposed for 24 hours to 2700 or 3400 lux light. Electroretinograms were recorded before exposure and/or treatment, at 1 day (D1) and 15 days (D15) after light-exposure to calculate Bmax (maximal b-wave amplitude). After the last ERG, rats were sacrificed and the outer nuclear layer thickness measured. Unexposed animals were processed in parallel.
Caspase-12 activity from untreated retina at 0h was set as 100%. At 0h, DMSO has no effect but Z-ATAD-FMK reduced caspase-12 activity to 52 %. At 2h of light exposure caspase-12 activity was reduced to 62 % in untreated and to 52 % in Z-ATAD-FMK retinas while it increased to 154 % in DMSO ones. At 24h, caspase-12 activity was back to the basal level in all groups. In unexposed rats, DMSO and Z-ATAD-FMK have no effect on retinal function or structure. In untreated retinas exposed to 2700 lux, the ONL in the superior part of the retina was reduced by 32% and Bmax by 33 %. DMSO was not different from untreated. Z-ATAD-FMK retinas were more preserved than DMSO. In untreated retinas exposed to 3400 lux, ONL in the superior part of the retina was reduced by 62% and Bmax by 52%. DMSO or Z-ATAD-FMK groups were not significantly different from untreated one.
We have shown that the caspase-12 inhibitor Z-ATAD-FMK reaches the retina and inhibits caspase-12 activity at least at the beginning of light exposure. In these conditions, caspase-12 inhibition can protect the retina from weak light-stress Further experiments are on course to determine if an increase in caspase-12 inhibition increase its neuroprotective effect.
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