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Updated: Jun 13, 2026
Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
ERK1/2 signaling pathways involved in VEGF release in diabetic rat retina
Xiaofeng Ye1, Gezhi Xu, Qing Chang
1EENT Hospital, Eye Institute, Fudan University, Shanghai, China.
Purpose:
Vascular endothelial growth factor (VEGF) is one of the major factors promoting diabetic retinopathy (DR). A better understanding of the signaling pathway in VEGF regulation is of clinical importance to identify more precise therapeutic targets for diabetic retinopathy. The ERK1/2 signaling pathway has been shown to play a key role in some oncoma and hematologic diseases by mediating VEGF release. This research was conducted to determine whether the ERK1/2 signaling pathway also plays a major role in VEGF release in DR development.
Methods:
One hundred Sprague-Dawley (SD) rats were induced to diabetes by streptozotocin (STZ) injection and monitored at several time points (1, 2, 3, 4, 8, and 12 weeks) for ERK1/2 phosphorylation, Activator protein (AP)-1 activity and concentration, and VEGF protein and mRNA expression, using immunohistochemical and biochemical methods. RESULTS. The ERK1/2 signaling pathway was rapidly activated 1 week after diabetes was induced. AP-1, the downstream transcription factor of ERK1/2, was also activated, and VEGF became highly regulated in a similar trend. U0126, an inhibitor of ERK1/2, also downregulated VEGF expression, in addition to ERK1/2 and AP-1 activity.
Conclusions:
ERK1/2 signaling pathway is involved in VEGF release in diabetic rat retina; therefore, ERK1/2 may be a potential therapeutic target of DR.
Insights
The ERK1/2 signaling pathway activates vascular endothelial growth factor (VEGF) release in diabetic retinopathy (DR). Inhibiting ERK1/2 reduces VEGF, suggesting it as a therapeutic target for DR.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss, driven by vascular endothelial growth factor (VEGF).
- Understanding VEGF regulation is crucial for developing targeted therapies for DR.
- The ERK1/2 signaling pathway is implicated in VEGF release in other diseases.
Purpose of the Study:
- To investigate the role of the ERK1/2 signaling pathway in VEGF release during diabetic retinopathy development.
- To determine if ERK1/2 activation contributes to VEGF upregulation in the diabetic retina.
Main Methods:
- Streptozotocin-induced diabetes in 100 Sprague-Dawley rats.
- Assessment of ERK1/2 phosphorylation, AP-1 activity, and VEGF expression (protein and mRNA) over 12 weeks.
- Utilized immunohistochemical and biochemical techniques.
- Employed U0126, an ERK1/2 inhibitor, to assess its effect on VEGF levels.
Main Results:
- ERK1/2 signaling pathway activation was observed as early as 1 week post-diabetes induction.
- Downstream Activator protein (AP)-1 activation and increased VEGF expression followed a similar trend.
- Inhibition of ERK1/2 with U0126 led to decreased ERK1/2 and AP-1 activity, and downregulated VEGF expression.
Conclusions:
- The ERK1/2 signaling pathway is significantly involved in VEGF release within the diabetic rat retina.
- ERK1/2 represents a potential therapeutic target for managing diabetic retinopathy.
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