Differential Cell Death and Bcl-2 Expression in Mouse Retina after Glutathione Decrease by Systemic D,L-Buthionine Sulphoximine Administration

다국어 초록 (Multilingual Abstract)

Glutathione (GSH) plays a critical role in cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH decrease using [D, L]-buthionine sulphoximine (BSO) induces retinal cell death, but the underlying mechanisms of this are still unclear. Here, we demonstrated that retinal GSH level is closely related to retinal cell death as well as expression of an anti-apoptotic molecule, Bcl-2, in the retina. We induced differential expression of retinal GSH by single and multiple administrations of BSO, and examined retinal GSH levels and retinal cell death in vivo. Single BSO administration showed a transient decrease in the retinal GSH level, whereas multiple BSO administration showed a persistent decrease in the retinal GSH level. Retinal cell death also showed similar patterns: transient increase of retinal cell death was observed after single BSO administration, whereas persistent increase of retinal cell death was observed after multiple BSO administration. Changes in the retinal GSH level affected Bcl-2 ex-pression in the retina. Immunoblot and immunohisto-chemical ana-lyses showed that single and multiple ad-ministration of BSO induced differential expressions of Bcl-2 in the retina. Taken together, the results of our study suggest that the retinal GSH is important for the survival of retinal cells, and retinal GSH appears to be deeply related to Bcl-2 expression in the retina. Thus, alteration of Bcl-2 expression may provide a therapeutic tool for retinal degenerative diseases caused by retinal oxidative stress such as glaucoma or retinopathy.

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