Long-term multimodal imaging of persistent retinal neovascularization using DL-alpha-aminoadipic acid in pigmented and white rabbits

Abstract

Purpose : Intravitreal (IVT) injection of DL-alpha-aminoadipic acid (DL-AAA) is a new animal model for persistent retinal neovascularization (RNV) reported in rabbits. This study performs longitudinal multimodal imaging for up to 52 weeks to evaluate DL-AAA RNV in both New Zealand white (NZW) rabbits and Dutch-Belted pigmented (DBP) rabbits.

Methods : Detailed characterization and quantification of this model were performed in these two strains in 32 eyes by optical coherence tomography (OCT), fundus photography, and fluorescein angiography (FA) for up to 16 weeks following DL-AAA administration in 32 eyes and up to 52 weeks in 5 eyes. H & E histology was also performed 8 weeks after injection of DL-AAA.

Results : RNV was successfully generated using 50 μL 80mM DL-AAA solution for DBP rabbits and 80 μL 80mM DL-AAA for NZW rabbits. The incidence of persistent vascular leakage is 100% (15/15) for DBP rabbits and 70.6% (12/17) for NZW rabbits at 16 weeks. Complications with NZW rabbits ultimately decreased the efficiency in NZW rabbits to 58.8% (10/17) of NZW rabbits getting persistent (to 16 weeks) vascular leakage without ocular complications as compared with 100% (15/15) in DBP rabbits. Five eyes (2 DBP and 3 NZW) were selected from those demonstrating RNV at 16 weeks and were monitored for up to 52 weeks. All 5 demonstrated persistent RNV to 52 weeks. Quantification of the mean leakage area (MLA) in NZW rabbits is more challenging than in DBP rabbits due to reduced contrast between the leakage and background in NZW rabbits.

Conclusions : DL-AAA can induce persistent and quantifiable RNV in both DBP and NZW rabbits. DBP rabbits have a higher success rate, lower required volume of DL-AAA, and less challenging method for quantification that could be more desirable.

This is a 2021 ARVO Annual Meeting abstract.