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Role of microRNA-29a in the development of diabetic retinopathy by targeting AGT gene in a rat model
Li-Qiong Zhang1, Hao Cui1, Lin Wang1
1Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin 150001, PR China.
Objectives:
This study intends to explore the role of microRNA-29a (miRNA-29a) in the development of diabetic retinopathy by targeting AGT gene in a rat model.
Methods:
Fifty-six DR rat models were established and divided into 7 groups (with 8 rats in each group): the model group, the miRNA-29a group, the miRNA-29a knockdown group, the negative control (NC) group, the AGT group, the miRNA-29a+AGT group, and the miRNA-29a knockdown+AGT group respectively, while 8 normal rats were selected as the normal group. The qRT-PCR was used to detect the expression of miRNA-29a and AGT mRNA. The AGT protein expression was measured using Western blotting. The ADPase histochemical staining was applied to detect retinal neo-vascular morphology. The number of retinal vascular endothelial cells was counted by H&E staining.
Results:
MiRNA-29a and AGT mRNA expressions were negatively correlated. Compared with rats in the normal group, the miRNA-29a expression in DR rats of each group decreased, but the AGT mRNA and protein expression increased; the vascular distribution was in disorder, and the new retinal vessels, vascular density, and endothelial nuclei all increased. Compared with the model group, miRNA-29a increased, and the AGT mRNA and protein expression decreased in the miRNA-29a group; additionally, the vascular density, tortuosity, and endothelial cell nuclei significantly decreased. The opposite trend was found in the miRNA-29a knockdown group, the miRNA-29a knockdown+AGT group, and the AGT group, particularly in the miRNA-29a knockdown+AGT group.
Conclusion:
Overexpression of miRNA-29a could down-regulate AGT expression, thereby preventing the development of DR in a rat model.
Insights
MicroRNA-29a (miRNA-29a) plays a crucial role in diabetic retinopathy (DR). Upregulating miRNA-29a can reduce AGT expression and prevent DR development in a rat model.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- The role of microRNA-29a (miRNA-29a) and its target gene, AGT, in DR pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of miRNA-29a in diabetic retinopathy development.
- To explore the regulatory effect of miRNA-29a on the AGT gene in a rat model.
Main Methods:
- Established 56 diabetic retinopathy rat models and divided them into 7 groups.
- Utilized qRT-PCR, Western blotting, and H&E staining to analyze miRNA-29a, AGT expression, and retinal vascular changes.
Main Results:
- DR rats showed decreased miRNA-29a and increased AGT expression, with disordered retinal vasculature.
- Overexpression of miRNA-29a in DR rats led to decreased AGT expression and improved retinal vascular morphology.
- Knockdown of miRNA-29a exacerbated DR, while AGT group showed opposite trends.
Conclusions:
- MiRNA-29a is downregulated in diabetic retinopathy.
- Overexpression of miRNA-29a can down-regulate AGT expression, offering a potential therapeutic strategy for DR.
