VEGF-induced Retinal Leakage

Summary: The up-regulation of VEGF leads to abnormal retinal vascular growth and leakage that causes visual impairment. Intravitreal injection of VEGF causes a transient retinal leakage mimicking the like of wet AMD and diabetic retinopathy.

Model Description

Vascular endothelial growth factor (VEGF) is up regulated in wet AMD and diabetic retinopathy. This up-regulation leads to abnormal retinal vascular growth and leakage that causes visual impairment. Intravitreal injection of VEGF causes a transient retinal leakage mimicking the disease.

At Experimentica, we have fully implemented and validated rabbit VEGF-induced retinal leakage model with a clinically relevant reference compound and the most comprehensive list of read-outs.

Animal speciesRabbits
Method of inductionInjection of vascular endothelial growth factor (VEGF)
Follow-up periodTypically up to 14 days
Route of compound administrationIntravitreal, topical, systemic
Read-outs1. In vivo imaging:
– Qualitative grading of retinal leakage (fluorescein angiography);
2. Histology:
Post-mortem assessment of morphological changes both qualitatively and quantitatively.

Outcomes and Read-Outs

In vivo imaging

Fluorescein angiography (rabbit; Heideleberg Spectralis). Retinal vascular leakage and leakage suppression can be imaged after VEGF induction and treatment

Fig. 1. High-resolution imaging using fluorescein angiography (FA).
Fig. 1. High-resolution imaging using fluorescein angiography (FA). FA images from vascular endothelial growth factor (VEGF) induced retinal leakage in rabbits are shown. Image in the top row shows a control vasculature FA in a rabbit. Images in the second row show day 3 images of  vascular leakage in a VEGF-induced eye treated with saline. Images in the third row show day 3 images of vascular leakage suppression in a representative VEGF-induced eye treated with Avastin®.

Dose range VEGF study showing the optimal dosage for retinal leakage.

Fig. 2. Vascular Endothelial Growth Factor (VEGF) dosage range study for retinal leakage induction.
Fig. 2. Vascular endothelial growth factor (VEGF) dose-ranging study for retinal leakage induction. A. Mean leakage scores from fluorescein angiography images graded 3 days post VEGF induction. B. Mean leakagescores from fluorescein angiography images graded 7 days post VEGF induction. * ANOVA (p<0.05).

References

  • Neverauskas D. In vivo imaging of VEGF-induced retinal neovascularization in Rabbits. Experimentica webinar series, May 20th, 2020.

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