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Biochemistry & Bioanalytical

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VEGF-induced Retinal Leakage

Age-related macular degeneration is a leading cause of blindness that can be characterized by a decrease in sharp and central vision due to damage in the macular region of the retina.1 This disease can be broken down into two types, wet and dry, with the wet form having a more rapid onset and involving the abnormal growth of retinal blood vessels. The wet AMD model serves to reproduce this pathology through intravitreal administration of vascular epithelial growth factor (VEGF). Successful disease induction is supported by a variety of longitudinal ocular imaging modalities and biomarker analyses, thereby making this an ideal model for therapeutic interventions.

Animal SpeciesRabbit
Method of Induction Intravitreal injection of VEGF
Follow up Period Acutely through 2 - 3 weeks
Route of intervention Intravitreal, intracameral, topical, systemic
Readouts
  • Fluorescein angiography
  • Optical coherence tomography
  • Ocular examinations by board-certified veterinary ophthalmologist
  • Immunofluorescence, immunohistochemistry and H&E staining
  • Biomarker analysis via qPCR or ligand binding assay
Figure 1: Intravitreal Injection
  • Optical Coherence Tomography (OCT) – OCT imaging allows for longitudinal cross-section scans of the retina to be collected. In addition to being able to measure changes related to angiogenesis, this technique allows for the assessment of the inflammatory response induced by the VEGF injection and the effect that potential therapeutic candidates have on this response.
  • Fluorescein Angiography (FA) – FA imaging allows for real-time and longitudinal assessment of retinal leakage through intravenous injection of sodium fluorescein. FA data can then be analyzed to quantitate the leakage induced and assess the potential benefit of therapeutic candidates.
  • VEGF Dose Response Curve - Leakage characteristics, disease duration and clinical observations have been analyzed for a range of VEGF165 doses to allow for selection of an optimal dose level to best meet client and therapeutic needs.
  • Positive Treatment Group - Using a commercially available anti-VEGF, a study design has been established for disease induction and positive control intervention that can be applied and modified for treatments intended for acute wet AMD applications.
    Reference:
    • 1. Centers for Disease Control and Prevention. (2023, August 23). Common eye disorders and diseases. Centers for Disease Control and Prevention. https://www.cdc.gov/visionhealth/basics/ced/index.html#AMD

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