ADP-ribosylation factor as a novel target for corneal neovascularization regression
Chunyan Dai1, Gaoqin Liu, Longbiao Li
1Department of Ophthalmology, the First Affiliated Hospital of Soochow University, China PR.
Purpose:
To evaluate the roles of ADP-ribosylation factor (ARF) in alkali-induced corneal neovascularization (CNV).
Methods:
CNV was induced by alkali injury and compared in ARF1 inhibitor- or vehicle-treated mice 3 weeks after injury. Angiogenic and apoptosis factor expression in corneas after injury was quantified with reverse-transcription PCR. Human retinal endothelial cell apoptosis induced by ARF1 inhibitor was detected with flow cytometry.
Results:
The mRNA expression of ARF1 was augmented in the corneas after alkali injury. Compared with vehicle-treated mice, ARF1 inhibitor-treated mice exhibited impaired CNV 3 weeks after injury, as evidenced by corneal whole mount CD31-staining. Concomitantly, the enhancement of intraocular vascular endothelial growth factor expression was reduced in ARF1 inhibitor-treated mice compared to control mice after injury. Moreover, local administration of the ARF1 inhibitor after alkali injury enhanced intraocular caspase-3 expression. ARF1 inhibitor treatment can significantly induce human retinal endothelial cell apoptosis.
Conclusions:
The ARF1 inhibitor can induce the regression of alkali-induced CNV through increased endothelial cell apoptosis and downregulated intracorneal VEGF expression. ARF1 is an effective intervention target for CNV.
Insights
ADP-ribosylation factor 1 (ARF1) inhibition reduces alkali-induced corneal neovascularization (CNV) by promoting endothelial cell apoptosis and decreasing vascular endothelial growth factor (VEGF). ARF1 is a potential therapeutic target for CNV.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cell Biology
Background:
- Corneal neovascularization (CNV) is a pathological process involving the growth of new blood vessels in the cornea.
- Alkali burns are a common cause of severe corneal injury and subsequent neovascularization.
- Understanding the molecular mechanisms underlying CNV is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of ADP-ribosylation factor (ARF) in the development of alkali-induced corneal neovascularization (CNV).
- To evaluate the therapeutic potential of targeting ARF1 in CNV.
Main Methods:
- Corneal neovascularization was induced in mice using alkali injury.
- Mice were treated with an ARF1 inhibitor or a vehicle control.
- Gene expression of angiogenic and apoptotic factors was analyzed using reverse-transcription PCR.
- Human retinal endothelial cell apoptosis was assessed via flow cytometry.
Main Results:
- ARF1 mRNA expression was upregulated in corneas following alkali injury.
- ARF1 inhibitor treatment significantly reduced CNV and vascular endothelial growth factor (VEGF) expression.
- Treatment with the ARF1 inhibitor increased caspase-3 expression in the cornea.
- ARF1 inhibition induced apoptosis in human retinal endothelial cells.
Conclusions:
- ADP-ribosylation factor 1 (ARF1) plays a significant role in alkali-induced corneal neovascularization (CNV).
- Inhibition of ARF1 promotes regression of CNV by enhancing endothelial cell apoptosis and downregulating intracorneal VEGF.
- ARF1 represents a promising therapeutic target for managing CNV.
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