DL-AAA-induced Retinal Neovascularization and Chronic Leakage

Summary: DL-AAA induces retinal neovascularization and chronic retinal vasculature leakage similar to patients with advanced neovascular wet AMD. 

Model Description

DL-2-aminoadipic acid (DL-AAA) is a retinal glial cell toxin that has been shown to induce retinal neovascularization and chronic retinal vasculature leakage very similar to patients with advanced neovascular (“wet”) AMD.  DL-AAA is injected intravitreally (IVT) and over a period of 10 weeks new vessels sprout from the central retinal vasculature and remain permeable. The central retinal vasculature of the rabbit covers an area that is devoid of neural retina, therefore, animals that received DL-AAA retain significant vision despite the presence of significant vascular leak and retinal leakage,  which persist up to 24 months in rabbit eyes. This model is considered “the best Wet AMD model currently available”. 

At Experimentica, we have fully implemented and validated the rabbit DL-AAA model with clinically relevant reference compounds, bevacizumab (Avastin®) and aflibercept (Eylea®), and the most comprehensive list of read-outs. 

Animal speciesRabbits
Method of inductionDL-2-aminoadipic acid (DL-AAA)
Follow-up period10 weeks – 24 months
Route of compound administrationIntravitreal, topical, systemic
Read-outs1. In vivo imaging: qualitative grading of retinal leakage;
2. Flash electroretinography (fERG): functional deficits are observed both in a-wave and b-wave amplitudes;
3. Histology: retinal morphology and thickness

Outcomes and Read-Outs 

In vivo imaging

Fig. 1. High-resolution imaging using fluorescein angiography (FA). FA images from DL-2aminoadipic acid (DL-AAA) chronic retinal leakage rabbits are shown.
Fig. 1. High-resolution imaging using fluorescein angiography (FA). FA images from DL-2aminoadipic acid (DL-AAA) chronic retinal leakage rabbits are shown. Images in the top row show vascular leakage at week 11 post intravitreal (IVT) induction with DL-AAA (PRE). Images in the second-row show vascular leakage suppression  7 days after treatment with Avastin and 14 days after treatment with Eylea. 
Fig. 2. Leakage score and % of baseline leakage score in Avastin treated DL-AAA induced rabbits.
Fig. 2. Leakage score and % of baseline leakage score in Avastin treated DL-AAA induced rabbits. Leakage returns without re-induction within 3 months. 
Fig. 3. Leakage score in Eylea (Aflibercept 250 μg/eye) treated DL-AAA induced rabbits.
Fig. 3. Leakage score in Eylea (Aflibercept 250 μg/eye) treated DL-AAA induced rabbits. Leakage is suppressed in eyes treated with Aflibercept. 

Authors' picture