Glutathione depletion induces differential apoptosis in cells of mouse retina, in vivo.
Oxidative stress affects numerous intracellular macromolecules, and may result in cell death unless precisely regulated. Unregulated oxidative stress can be controlled by various cellular defense mechanisms such as glutathione (GSH) which can critically counteract the damaging effects of oxidative stress in mammalian cells. We determined the effects of unregulated oxidative stress induced by GSH depletion on cells in mouse retina. Mice were intraperitoneally injected with buthionine sulphoximine (BSO) at 1.5 g/kg. After 0, 1, 4, and 7 days of BSO administration, retinas were excised and sections were subjected to GSH assay and terminal uridine deoxynucleotidyl nick end labeling (TUNEL) analysis. After 4 days of BSO administration, the number of TUNEL positive cells was significantly increased. However, after 7 days, TUNEL positive cells returned to the basal level. The retinal region most affected by the BSO treatment appeared to be the outer nuclear layer where the photoreceptor cells reside. Different from cells in other regions, retinal cells in the inner nuclear layer increased in their apoptosis even after the first day of BSO injection, and the increase was further potentiated after 4 days. Taken together, our studies suggested that GSH depletion may cause unregulated oxidative stress to the cells in the retina and indeed increased cell death in the retina. The cells in the inner nuclear layer seemed to be affected earlier than the cells in other layers of the retina. The GSH level in the retina may be a crucial therapeutic target in preventing blindness.
Roh
Young-Jung
YJ
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, 62 Yeouido-Dong, Yeoungdeungpo-Ku, Seoul, 150-713, Seoul, Republic of Korea.
Moon
Cheil
C
Kim
So Yeun
SY
Park
Myoung Hee
MH
Bae
Yong Chul
YC
Chun
Myung-Hoon
MH
Moon
Jung-Il
JI
D000818:Animals; D000963:Antimetabolites / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000009:adverse effects; D002452:Cell Count; D005978:Glutathione / Q000172:deficiency*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000963:Antimetabolites; D019328:Buthionine Sulfoximine; D005978:Glutathione