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Updated: May 10, 2026
An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice
Published on: January 12, 2024
Triamcinolone acetonide inhibits p38MAPK activation and neuronal apoptosis in early diabetic retinopathy
1Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Lab, P.R. China. mmzxy@yahoo.com
Objective:
Intravitreal glucocorticoids and anti-vascular endothelial growth factor (VEGF) therapies are novel strategies for the treatment of advanced diabetic retinopathy, a condition with inflammatory and neuropathic elements. In contrast with anti-VEGF therapy, glucocorticoids may also exert neuroprotective effects. How glucocorticoids protect retinal neurons is unknown. The aims of the study are to investigate the anti-apoptotic actions of glucocorticoids on diabetic retinal neurons, and characterize the signalling pathways involved.
Research Design And Methods:
The regulation of gene expression of the four p38 mitogen-activated protein kinase (MAPK) isoforms (α, β, δ and γ) and the glucocorticoid receptor (GR) in the retinas was evaluated using quantitative RT-PCR, Western blot and immunohistochemistry. Phosphorylation of all isoforms p38MAPK (Thr180/Tyr182) and GR (S-211) was further evaluated. Apoptosis was confirmed by immunolocalization of active CASPASE-3 and the subsequent cleavage of poly (ADP-ribose) polymerase (PARP) following intravitreal injection of triamcinolone acetonide (IVTA), in an early diabetic rat model (26 days after induction of diabetes.
Results:
IVTA significantly down-regulated mRNA expression of Caspase 3. Activation of CASPASE-3, the subsequent cleavage of PARP-1 and phosphorylation of p38MAPK induced by diabetes were attenuated by IVTA treatment, concomitantly with activation by phosphorylation of the glucocorticoid receptor (GR S-211).
Conclusions:
IVTA activates the GR and exerts neural protective effects on retinal neurons. Inhibition of the p38MAPK pathway and activation of GR play a critical anti-apoptotic role in retinal neurons of diabetes following IVTA treatment. Both the anti-inflammatory and anti-apoptotic effects of glucocorticoids may be mediated through inhibition of the p38MAPK pathway in diabetic retinopathy.
Insights
Intravitreal triamcinolone acetonide (IVTA) protects diabetic retinal neurons by activating the glucocorticoid receptor (GR) and inhibiting the p38 MAPK pathway. This reduces apoptosis, offering a potential treatment for diabetic retinopathy.
Area of Science:
- Ophthalmology
- Neuroscience
- Endocrinology
Background:
- Diabetic retinopathy involves inflammation and neuropathy.
- Intravitreal glucocorticoids offer neuroprotection beyond anti-VEGF therapies.
- Mechanisms of glucocorticoid neuroprotection in diabetic retinopathy are unclear.
Purpose of the Study:
- Investigate glucocorticoid-induced anti-apoptotic effects on diabetic retinal neurons.
- Characterize the signaling pathways involved in glucocorticoid neuroprotection.
Main Methods:
- Quantitative RT-PCR, Western blot, and immunohistochemistry assessed p38 MAPK and GR expression.
- Phosphorylation of p38 MAPK and GR was evaluated.
- Apoptosis markers (active CASPASE-3, cleaved PARP) were assessed after IVTA in a diabetic rat model.
Main Results:
- IVTA significantly downregulated Caspase 3 mRNA.
- IVTA attenuated diabetes-induced CASPASE-3 activation, PARP-1 cleavage, and p38 MAPK phosphorylation.
- IVTA treatment led to glucocorticoid receptor (GR S-211) phosphorylation.
Conclusions:
- IVTA activates the GR, providing neuroprotection to retinal neurons.
- Inhibition of the p38 MAPK pathway and GR activation are key anti-apoptotic mechanisms.
- Glucocorticoid anti-inflammatory and anti-apoptotic effects in diabetic retinopathy may involve p38 MAPK inhibition.
