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Updated: Apr 9, 2026
Morphometric Analyses of Retinal Sections
Published on: February 19, 2012
Mechanisms Contributing to Inhibition of Retinal Ganglion Cell Apoptosis by AMPK in Experimental Glaucoma
Zhaolin Gao1,2,3,4, Haiyang Yu2,5, Tianqi Duan2,5
1Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract:
AMPK is AMP-activated protein kinase that plays a major role in regulating energy metabolism. AMPK has attracted widespread interest as a potential therapeutic target for neurodegenerative diseases. However, its effects on glaucoma remain unclear. Here, we established the oxygen-glucose deprivation/recovery (OGD/R) model and retinal ischemia-reperfusion injury (I/R) model to simulate the glaucomatous injury. Our results demonstrated that OGD/R induced apoptosis. Retinal I/R caused thinner retinas, retinal ganglion cells (RGCs) loss, and an increase in the number of apoptotic RGCs by using H-E staining, TUNEL staining, and immunofluorescence staining. A slight increase in phosphorylation-AMPK (p-AMPK) level and a significant upregulation in phosphorylated-mTOR (p-mTOR) level were detected in experimental glaucoma models. Activating AMPK led to the downregulation of p-mTOR, Bax, and cleaved-caspase 3, upregulation of Bcl-2 as well as inhibition of apoptosis. I/R induced the loss of RGCs and an increase in the number of apoptotic RGCs, which was markedly relieved by using AMPK activator. Inhibiting AMPK by Compound C reversed the effects, led to the inhibition of p-AMPK and the upregulation of p-mTOR as well as promoting apoptosis. These findings indicate that activating AMPK attenuates RGCs apoptosis in glaucoma models via inhibiting mTOR. This study suggests that AMPK may be a novel target for glaucoma treatment.
Insights
Activating AMP-activated protein kinase (AMPK) protects against glaucoma by reducing retinal ganglion cell apoptosis. This suggests AMPK is a promising therapeutic target for treating glaucoma.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- AMP-activated protein kinase (AMPK) regulates energy metabolism and is a potential therapeutic target for neurodegenerative diseases.
- The role of AMPK in glaucoma, a leading cause of irreversible blindness, is not well understood.
Purpose of the Study:
- To investigate the effects of AMPK activation and inhibition on retinal ganglion cell (RGC) apoptosis in experimental glaucoma models.
- To explore the potential of AMPK as a therapeutic target for glaucoma treatment.
Main Methods:
- Established oxygen-glucose deprivation/recovery (OGD/R) and retinal ischemia-reperfusion (I/R) injury models to simulate glaucomatous injury.
- Utilized H-E staining, TUNEL staining, and immunofluorescence to assess RGC apoptosis and retinal damage.
- Administered AMPK activators and inhibitors (Compound C) to evaluate their effects on cellular pathways and RGC survival.
Main Results:
- OGD/R and I/R models induced significant RGC apoptosis, thinner retinas, and RGC loss.
- Experimental glaucoma models showed increased phosphorylated-AMPK (p-AMPK) and phosphorylated-mTOR (p-mTOR) levels.
- AMPK activation inhibited mTOR signaling, reduced pro-apoptotic proteins (Bax, cleaved-caspase 3), increased anti-apoptotic protein (Bcl-2), and protected RGCs from apoptosis.
- AMPK inhibition exacerbated RGC apoptosis and increased p-mTOR levels.
Conclusions:
- AMPK activation attenuates RGC apoptosis in glaucoma models, primarily through the inhibition of mTOR signaling.
- AMPK represents a novel and promising therapeutic target for glaucoma treatment, offering neuroprotection to RGCs.
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