CIC-3 chloride channel blockade protects mouse photoreceptorderived 661W cells against ischemia-reperfusion-induced injury in vitro

다국어 초록 (Multilingual Abstract)

Exposure to ischemia/reperfusion leads to the development and progression of retinal degenerative diseases. However, the exact mechanisms are not fully understood. In this article, the role of CIC-3 chloride channel in OGD-R (oxygen-glucose deprivation followed by reperfusion)-induced retinal damage was examined. Mouse photoreceptor-derived 661W cells were treated with the CIC-3 antisense oligonucleotide before exposure to OGD-R. Cell viability, mitochondrial membrane potential, cytochrome-c level, DNA fragmentation, caspase activity and protein expression were detected. Pretreatment of 661W cells with CIC- 3 antisense oligonucleotide significantly decreased OGD-R-mediated toxicity. In addition, apoptosis-related biochemical indicators showed that pre-incubation of CIC-3 antisense oligonucleotide would elevate the mitochondrial membrane potential, decrease the release of cytochrome-c as well as formation of DNA fragmentation, and inhibit activities of caspase-3 and caspase- 9 in exogenous OGD-R-treated 661W cells. Moreover, treatment with CIC-3 antisense oligonucleotide changed the expression of apoptosis-related protein.
These results suggest that CIC-3 chloride channel mediates OGD-R-induced apoptosis, at least partially through mitochondrial membrane potential pathway and increasing the levels of proapoptotic molecules in 661W cells. CIC-3 chloride channel blockade may provide a new therapeutic approach for preventing ischemia/reperfusion- induced retinal neural damage.

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