July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Characterization of angiographic features and validation of a chronic wet AMD rabbit model induced by DL-AAA
Author Affiliations & Notes
  • Vatsala Naageshwaran
    Absorption Systems, San Diego, California, United States
  • Footnotes
    Commercial Relationships   Vatsala Naageshwaran, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1250. doi:
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      Vatsala Naageshwaran; Characterization of angiographic features and validation of a chronic wet AMD rabbit model induced by DL-AAA. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1250.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : DL-2-aminoadipic acid (DL-AAA), a retinal glial (Müller) cell toxin, has been shown to induce retinal neovascularization (RNV) and chronic retinal vasculature leakage after intravitreal (IVT) administration. Here, we have extensively characterized DL-AAA induced angiographic features in Dutch Belted (DB) rabbit eyes and established suitability of this model to test anti-neovascular therapies.

Methods : DL-AAA (80mM) was administered intravitreally in both eyes of DB rabbit. After IVT administration, clinical ophthalmic examinations were performed weekly following modified McDonald-Shadduck Scoring System. Color fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT) were performed every two weeks until stable retinal vascular leakage was determined. Once stable retinal leakage occurred, anti VEGF (Avastin, Lucentis and Eylea) and anti-inflammatory (TAA) drugs were tested for their efficacy via IVT injection. Fluorescein angiograms were scored before and after treatment.

Results : All DL-AAA injected eyes resulted in epiretinal membrane formation and retinal vascular leakage as early as one week post DL-AAA administration. Severe retinal vascular leakage from dilated and tortuous vessels was observed at 4 weeks and became stable by 12 weeks post DL-AAA administration. Color fundus photography showed complete loss of medullary rays and hemorrhage from epiretinal membrane in all eyes. Follow-up retinal OCT scans showed increased infiltration of inflammatory cells in the vitreous and retina. Retinal degeneration starts as early as one week post DL-AAA injection. Complete degeneration of retina including photoreceptors and neuronal layers was observed by week 8 post DL-AAA injection. Vascular dilation, RNV and retinal degeneration were more prominent in area centralis region. IVT administration of all three anti VEGF drugs suppressed retinal leakage 6 to 8 week and returns to pre-treatment levels after wash out of drugs. Anti-inflammatory TAA administration was found to be less effective than anti VEGF drugs.

Conclusions : DL-AAA rabbit model mimics wet AMD angiographic features like retinal neovascularization and chronic retinal leakage. This model will serve as an invaluable tool to test therapeutic efficacy and duration of action of novel anti-neovascular formulations, alone or in combination with anti-inflammatory compounds.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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