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Stanniocalcin-1 protects retinal ganglion cells by inhibiting apoptosis and oxidative damage.

Kim SJ, Ko JH, Yun JH, Kim JA, Kim TE, Lee HJ, Kim SH, Park KH, Oh JY - PLoS ONE (2013)

Bottom Line: We found that intravitreal injection of STC-1 increased the number of RGCs in the retina at days 7 and 14 after ONT, and decreased apoptosis and oxidative damage.In cultures, treatment with STC-1 dose-dependently increased cell viability, and decreased apoptosis and levels of reactive oxygen species in RGC-5 cells that were exposed to CoCl2.The expression of HIF-1α that was up-regulated by injury was significantly suppressed in the retina and in RGC-5 cells by STC-1 treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea.

ABSTRACT
Optic neuropathy including glaucoma is one of the leading causes of irreversible vision loss, and there are currently no effective therapies. The hallmark of pathophysiology of optic neuropathy is oxidative stress and apoptotic death of retinal ganglion cells (RGCs), a population of neurons in the central nervous system with their soma in the inner retina and axons in the optic nerve. We here tested that an anti-apoptotic protein stanniocalcin-1 (STC-1) can prevent loss of RGCs in the rat retina with optic nerve transection (ONT) and in cultures of RGC-5 cells with CoCl2 injury. We found that intravitreal injection of STC-1 increased the number of RGCs in the retina at days 7 and 14 after ONT, and decreased apoptosis and oxidative damage. In cultures, treatment with STC-1 dose-dependently increased cell viability, and decreased apoptosis and levels of reactive oxygen species in RGC-5 cells that were exposed to CoCl2. The expression of HIF-1α that was up-regulated by injury was significantly suppressed in the retina and in RGC-5 cells by STC-1 treatment. The results suggested that intravitreal injection of STC-1 might be a useful therapy for optic nerve diseases in which RGCs undergo apoptosis through oxidative stress.

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Related in: MedlinePlus

STC-1 inhibited apoptosis of RGC-5 cells exposed to CoCl2.(A) MTT assay showed that exposure to CoCl2 for 12 h decreased the viability of RGC-cells in a concentration-dependent manner. (B) STC-1 treatment significantly rescued RGC-5 cells that were injured by either 200 μM or 400 μM CoCl2 in a dose-dependent manner. (C, D) Flow cytometry showed that CoCl2 increased the numbers of PI+Annexin+ cells in RGC-5 cells in concentration- and time-dependent manners. (E, F) Both 100 and 500 ng/mL of STC-1 decreased the numbers of PI+Annexin+ cells in RGC-5 cells injured by 200 μM CoCl2. The values are presented as the mean ± SEM.
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pone-0063749-g003: STC-1 inhibited apoptosis of RGC-5 cells exposed to CoCl2.(A) MTT assay showed that exposure to CoCl2 for 12 h decreased the viability of RGC-cells in a concentration-dependent manner. (B) STC-1 treatment significantly rescued RGC-5 cells that were injured by either 200 μM or 400 μM CoCl2 in a dose-dependent manner. (C, D) Flow cytometry showed that CoCl2 increased the numbers of PI+Annexin+ cells in RGC-5 cells in concentration- and time-dependent manners. (E, F) Both 100 and 500 ng/mL of STC-1 decreased the numbers of PI+Annexin+ cells in RGC-5 cells injured by 200 μM CoCl2. The values are presented as the mean ± SEM.

Mentions: To evaluate the effect of STC-1 on the survival of RGCs in vitro, we exposed RGC-5 cells to different concentrations of CoCl2 (0–800 μM) for 12 or 24 h in order to induce hypoxia and apoptosis. Expectedly, CoCl2 decreased the cell viability, and STC-1 treatment significantly increased the cell viability in a dose-dependent manner as measured by MTT assay (Fig. 3A, B). Also, flow cytometry showed that the numbers of PI+Annexin+ cells indicating apoptotic cells were increased in RGC-5 cells after CoCl2 exposure in concentration and time-dependent manners (Fig. 3C, D). Treatment with either 100 or 500 ng/mL STC-1 significantly decreased the numbers of PI+Annexin+ cells as assayed by flow cytometry (Fig. 3E, F).


Stanniocalcin-1 protects retinal ganglion cells by inhibiting apoptosis and oxidative damage.

Kim SJ, Ko JH, Yun JH, Kim JA, Kim TE, Lee HJ, Kim SH, Park KH, Oh JY - PLoS ONE (2013)

STC-1 inhibited apoptosis of RGC-5 cells exposed to CoCl2.(A) MTT assay showed that exposure to CoCl2 for 12 h decreased the viability of RGC-cells in a concentration-dependent manner. (B) STC-1 treatment significantly rescued RGC-5 cells that were injured by either 200 μM or 400 μM CoCl2 in a dose-dependent manner. (C, D) Flow cytometry showed that CoCl2 increased the numbers of PI+Annexin+ cells in RGC-5 cells in concentration- and time-dependent manners. (E, F) Both 100 and 500 ng/mL of STC-1 decreased the numbers of PI+Annexin+ cells in RGC-5 cells injured by 200 μM CoCl2. The values are presented as the mean ± SEM.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646795&req=5

pone-0063749-g003: STC-1 inhibited apoptosis of RGC-5 cells exposed to CoCl2.(A) MTT assay showed that exposure to CoCl2 for 12 h decreased the viability of RGC-cells in a concentration-dependent manner. (B) STC-1 treatment significantly rescued RGC-5 cells that were injured by either 200 μM or 400 μM CoCl2 in a dose-dependent manner. (C, D) Flow cytometry showed that CoCl2 increased the numbers of PI+Annexin+ cells in RGC-5 cells in concentration- and time-dependent manners. (E, F) Both 100 and 500 ng/mL of STC-1 decreased the numbers of PI+Annexin+ cells in RGC-5 cells injured by 200 μM CoCl2. The values are presented as the mean ± SEM.
Mentions: To evaluate the effect of STC-1 on the survival of RGCs in vitro, we exposed RGC-5 cells to different concentrations of CoCl2 (0–800 μM) for 12 or 24 h in order to induce hypoxia and apoptosis. Expectedly, CoCl2 decreased the cell viability, and STC-1 treatment significantly increased the cell viability in a dose-dependent manner as measured by MTT assay (Fig. 3A, B). Also, flow cytometry showed that the numbers of PI+Annexin+ cells indicating apoptotic cells were increased in RGC-5 cells after CoCl2 exposure in concentration and time-dependent manners (Fig. 3C, D). Treatment with either 100 or 500 ng/mL STC-1 significantly decreased the numbers of PI+Annexin+ cells as assayed by flow cytometry (Fig. 3E, F).

Bottom Line: We found that intravitreal injection of STC-1 increased the number of RGCs in the retina at days 7 and 14 after ONT, and decreased apoptosis and oxidative damage.In cultures, treatment with STC-1 dose-dependently increased cell viability, and decreased apoptosis and levels of reactive oxygen species in RGC-5 cells that were exposed to CoCl2.The expression of HIF-1α that was up-regulated by injury was significantly suppressed in the retina and in RGC-5 cells by STC-1 treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea.

ABSTRACT
Optic neuropathy including glaucoma is one of the leading causes of irreversible vision loss, and there are currently no effective therapies. The hallmark of pathophysiology of optic neuropathy is oxidative stress and apoptotic death of retinal ganglion cells (RGCs), a population of neurons in the central nervous system with their soma in the inner retina and axons in the optic nerve. We here tested that an anti-apoptotic protein stanniocalcin-1 (STC-1) can prevent loss of RGCs in the rat retina with optic nerve transection (ONT) and in cultures of RGC-5 cells with CoCl2 injury. We found that intravitreal injection of STC-1 increased the number of RGCs in the retina at days 7 and 14 after ONT, and decreased apoptosis and oxidative damage. In cultures, treatment with STC-1 dose-dependently increased cell viability, and decreased apoptosis and levels of reactive oxygen species in RGC-5 cells that were exposed to CoCl2. The expression of HIF-1α that was up-regulated by injury was significantly suppressed in the retina and in RGC-5 cells by STC-1 treatment. The results suggested that intravitreal injection of STC-1 might be a useful therapy for optic nerve diseases in which RGCs undergo apoptosis through oxidative stress.

Show MeSH
Related in: MedlinePlus