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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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Intravitreal STC-1 administration decreased apoptosis and oxidative damage in the retina after optic nerve transection.(A–C) ELISA analysis showed that levels of active caspase-3 and two markers for oxidative damage (nitrotyrosine and protein carbonyl) were significantly decreased in the retina by an intravitreal injection of STC-1. (D, E) Real time RT-PCR indicated that levels of transcripts for HIF-1α and caspase-3 were increased in the retinas at day 1 after injury and significantly decreased by STC-1 treatment. The expression of caspase-3 was also significantly lower in the STC-1-treated retinas at day 7. (F) Western blot analysis confirmed that the expression of HIF-1α protein was increased in the retina at day 1 after ONT, and decreased by STC-1 injection. (G) The protein levels of UCP2 in the retina were decreased by ONT and not changed by STC-1 treatment. The values are presented as the mean ± SEM.
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pone-0063749-g002: Intravitreal STC-1 administration decreased apoptosis and oxidative damage in the retina after optic nerve transection.(A–C) ELISA analysis showed that levels of active caspase-3 and two markers for oxidative damage (nitrotyrosine and protein carbonyl) were significantly decreased in the retina by an intravitreal injection of STC-1. (D, E) Real time RT-PCR indicated that levels of transcripts for HIF-1α and caspase-3 were increased in the retinas at day 1 after injury and significantly decreased by STC-1 treatment. The expression of caspase-3 was also significantly lower in the STC-1-treated retinas at day 7. (F) Western blot analysis confirmed that the expression of HIF-1α protein was increased in the retina at day 1 after ONT, and decreased by STC-1 injection. (G) The protein levels of UCP2 in the retina were decreased by ONT and not changed by STC-1 treatment. The values are presented as the mean ± SEM.

Mentions: To investigate that STC-1 improved RGC survival by decreasing apoptosis, we analyzed the retina for the level of active caspase-3. Caspase-3 is implicated in the primary and secondary waves of RGC apoptosis and active for a long period of time and with a great intensity during RGC loss [23], [24]. As shown in Fig. 2A, caspase-3 activity at day 1 was significantly lower in the retinas of rats that received STC-1 compared to controls, indicating reduction of apoptosis by STC-1. Next, we assayed the retinas for nitrotyrosine and protein carbonyl, two protein derivatives of ROS that are used to measure oxidative damage in the retina [25], [26]. We evaluated ROS levels because previous studies reported that bursts of ROS were generated following ONT and triggered RGC apoptosis [2], [4]–[6]. The levels of both nitrotyrosine and protein carbonyl in the retinas at day 1 were significantly lower in STC-1-treated eyes compared to PBS-injected controls (Fig. 2B, C).


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)

Intravitreal STC-1 administration decreased apoptosis and oxidative damage in the retina after optic nerve transection.(A–C) ELISA analysis showed that levels of active caspase-3 and two markers for oxidative damage (nitrotyrosine and protein carbonyl) were significantly decreased in the retina by an intravitreal injection of STC-1. (D, E) Real time RT-PCR indicated that levels of transcripts for HIF-1α and caspase-3 were increased in the retinas at day 1 after injury and significantly decreased by STC-1 treatment. The expression of caspase-3 was also significantly lower in the STC-1-treated retinas at day 7. (F) Western blot analysis confirmed that the expression of HIF-1α protein was increased in the retina at day 1 after ONT, and decreased by STC-1 injection. (G) The protein levels of UCP2 in the retina were decreased by ONT and not changed by STC-1 treatment. 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-g002: Intravitreal STC-1 administration decreased apoptosis and oxidative damage in the retina after optic nerve transection.(A–C) ELISA analysis showed that levels of active caspase-3 and two markers for oxidative damage (nitrotyrosine and protein carbonyl) were significantly decreased in the retina by an intravitreal injection of STC-1. (D, E) Real time RT-PCR indicated that levels of transcripts for HIF-1α and caspase-3 were increased in the retinas at day 1 after injury and significantly decreased by STC-1 treatment. The expression of caspase-3 was also significantly lower in the STC-1-treated retinas at day 7. (F) Western blot analysis confirmed that the expression of HIF-1α protein was increased in the retina at day 1 after ONT, and decreased by STC-1 injection. (G) The protein levels of UCP2 in the retina were decreased by ONT and not changed by STC-1 treatment. The values are presented as the mean ± SEM.
Mentions: To investigate that STC-1 improved RGC survival by decreasing apoptosis, we analyzed the retina for the level of active caspase-3. Caspase-3 is implicated in the primary and secondary waves of RGC apoptosis and active for a long period of time and with a great intensity during RGC loss [23], [24]. As shown in Fig. 2A, caspase-3 activity at day 1 was significantly lower in the retinas of rats that received STC-1 compared to controls, indicating reduction of apoptosis by STC-1. Next, we assayed the retinas for nitrotyrosine and protein carbonyl, two protein derivatives of ROS that are used to measure oxidative damage in the retina [25], [26]. We evaluated ROS levels because previous studies reported that bursts of ROS were generated following ONT and triggered RGC apoptosis [2], [4]–[6]. The levels of both nitrotyrosine and protein carbonyl in the retinas at day 1 were significantly lower in STC-1-treated eyes compared to PBS-injected controls (Fig. 2B, C).

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