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Insulin-Like Growth Factor Binding Protein-Related Protein 1 Inhibit Retinal Neovascularization in the Mouse Model of
Ping Zhang1, Hong Wang1, Hui Cao1
1Department of Ophthalmology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China .
Purpose:
To explore the inhibitory effect of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) on retinal angiogenesis and its underlying molecular mechanisms in the mouse model of oxygen-induced retinopathy (OIR).
Methods:
C57BL/6J mice were classified into three groups as control group, OIR nonintervention group, and OIR intervention group. Postnatal day 12 (P12) mice in OIR intervention group were received recombinant mouse IGFBP-rP1 (50, 100, and 200 ng/mL) intravitreal injection. Five days later, the proliferative neovascular responses were estimated by quantifying the new vessel areas in flattening retinal tissues stained by high molecular fluorescein isothiocyanate-dextran and counting the numbers of neovascular cell nuclei breaking through the internal limiting membrane in cross sections. Expressions of phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, and vascular endothelial growth factor (VEGF) proteins in retinal tissues were assessed by western blot analysis.
Results:
Irregular neovascularization, nonperfusion region, and fluorescence leakage were observed in OIR models. The expression of retinal p-ERK1/2 and VEGF proteins were significantly upregulated in OIR nonintervention group compared with control group. The area ratio of retinal new vessels and the number of neovascular cell nuclei in OIR intervention group both decreased significantly, following the downregulation of retinal p-ERK1/2 protein expression and VEGF protein expression in a dose-dependent manner. Moreover, there was no significant difference in retinal ERK1/2 protein expression.
Conclusions:
IGFBP-rP1 inhibits retinal angiogenesis by blocking ERK signaling pathway and downregulating VEGF expression in the mouse model of OIR. It highlights the potential importance of IGFBP-rP1 serving as a target of gene therapy for retinal neovascularization in the future.
Insights
Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) effectively inhibits retinal angiogenesis in a mouse model. This protein reduces new vessel growth by impacting ERK signaling and vascular endothelial growth factor (VEGF) expression.
Area of Science:
- Ophthalmology
- Molecular Biology
- Vascular Biology
Background:
- Retinal angiogenesis is crucial for vision but can lead to disease when dysregulated.
- Oxygen-induced retinopathy (OIR) is a common model for studying neovascular eye diseases.
- Understanding molecular mechanisms controlling retinal angiogenesis is vital for developing therapies.
Purpose of the Study:
- To investigate the inhibitory effect of IGFBP-rP1 on retinal angiogenesis in a mouse OIR model.
- To elucidate the underlying molecular mechanisms of IGFBP-rP1's action on retinal neovascularization.
Main Methods:
- C57BL/6J mice were used, divided into control, OIR, and OIR with IGFBP-rP1 intervention groups.
- Recombinant mouse IGFBP-rP1 was administered via intravitreal injection in the OIR intervention group.
- Retinal neovascularization was assessed by quantifying new vessel areas and counting neovascular nuclei; protein expression of p-ERK1/2 and VEGF was analyzed via Western blot.
Main Results:
- OIR models exhibited irregular neovascularization, nonperfusion, and leakage.
- Retinal p-ERK1/2 and VEGF expression were significantly upregulated in OIR mice.
- IGFBP-rP1 treatment dose-dependently reduced neovascularization and downregulated p-ERK1/2 and VEGF expression.
Conclusions:
- IGFBP-rP1 inhibits retinal angiogenesis by suppressing the ERK signaling pathway and reducing VEGF expression.
- IGFBP-rP1 shows potential as a therapeutic target for treating retinal neovascularization.
- Further research may explore IGFBP-rP1 for gene therapy applications in eye diseases.