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Updated: May 16, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Tissue kallikrein attenuates choroidal neovascularization via cleavage of vascular endothelial growth factor
Junichi Fukuhara1, Kousuke Noda, Miyuki Murata
1Laboratory of Ocular Cell Biology & Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Purpose:
To investigate the antiangiogenic properties of tissue kallikrein in a murine model of laser-induced choroidal neovascularization (CNV).
Methods:
CNV was induced in male C57BL/6J mice by laser photocoagulation. The animals received daily subcutaneous injections of tissue kallikrein (50 μg/kg) or vehicle control for 2 days before the laser photocoagulation, and this treatment continued until sample collection. Seven days after laser injury, the CNV size was quantified. The levels of monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 were assessed by enzyme-linked immunosorbent assay 3 days after laser injury. Cleavage of mouse VEGF with tissue kallikrein was assessed in vivo and in vitro. The protein levels of bradykinin were assessed in the RPE-choroid complexes and hearts.
Results:
A significant decrease in CNV size was observed in animals treated with tissue kallikrein (27,168.3 ± 2432.2 μm(2)) compared with vehicle-treated controls (36,374.6 ± 3204.1 μm(2), P < 0.05). Tissue kallikrein treatment significantly reduced MCP-1, ICAM-1, and IL-6 levels in RPE-choroid complexes. Furthermore, immunoblotting showed the bands, presumably corresponding to the fragmented VEGF(164) protein, in the samples of both mouse VEGF preincubated with tissue kallikrein and RPE-choroid complexes obtained from animals treated with tissue kallikrein. In addition, bradykinin was unchanged in the RPE-choroid complexes of animals treated with tissue kallikrein, whereas the level of bradykinin was increased in the heart obtained from these experimental animals.
Conclusions:
The current data indicate that kallikrein exhibits antiangiogenic properties by cleaving VEGF(164) in a laser-induced CNV model.
Insights
Tissue kallikrein demonstrated antiangiogenic effects by reducing choroidal neovascularization (CNV) size in mice. This effect is linked to kallikrein’s ability to cleave vascular endothelial growth factor (VEGF).
Area of Science:
- Ophthalmology
- Angiogenesis Research
- Biochemistry
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- Antiangiogenic therapies are crucial for managing CNV.
- Tissue kallikrein's role in angiogenesis requires further investigation.
Purpose of the Study:
- To evaluate the antiangiogenic potential of tissue kallikrein.
- To investigate tissue kallikrein's effect on laser-induced CNV in a murine model.
Main Methods:
- CNV was induced in mice using laser photocoagulation.
- Mice received daily subcutaneous injections of tissue kallikrein or vehicle.
- CNV size, inflammatory markers (MCP-1, ICAM-1, IL-6), VEGF cleavage, and bradykinin levels were assessed.
Main Results:
- Tissue kallikrein significantly reduced CNV size compared to controls.
- Kallikrein treatment decreased levels of MCP-1, ICAM-1, and IL-6.
- Evidence of vascular endothelial growth factor (VEGF) cleavage by kallikrein was observed in vivo and in vitro.
Conclusions:
- Tissue kallikrein exhibits significant antiangiogenic properties.
- Kallikrein's mechanism involves the cleavage of VEGF(164).
- This study supports kallikrein as a potential therapeutic agent for CNV.
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