June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Validation and characterization of a chronic model of retinal leakage in the Dutch Belted Rabbit using DL-AAA
Author Affiliations & Notes
  • Jeffrey Adam Jamison
    Ophthy-DS, Inc, Kalamazoo, Michigan, United States
  • Footnotes
    Commercial Relationships   Jeffrey Jamison, Ophthy-DS, Inc (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1993. doi:
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      Jeffrey Adam Jamison; Validation and characterization of a chronic model of retinal leakage in the Dutch Belted Rabbit using DL-AAA. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1993.

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

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Abstract

Purpose : To characterize and validate a model of retinal neovascularization (NV) and chronic leakage created by intravitreal injection of the glial toxin, DL-2-aminoadipic acid (DL-AAA) in the pigmented Dutch Belted rabbit. The anti-VEGF antibody Avastin was used to show temporary suppression of leakage and validate the model.

Methods : Procedures were done under isoflurane anesthesia. Animals were given 80ul of an 80 mM solution per eye of DL-AAA intravitreally on Day 0. IR fundus imaging, fluorescein angiography (FA), indocyan green angiography (ICG), and optical coherence tomography (OCT) was performed using the Heidelberg Spectralis cSLO at various times over 12 months. Once the retina developed stable leakage (~10 weeks), animals were administered 0.25 ug Avastin intravitreally and monitored for return to stable pathology.

Results : DL-AAA given intravitreally to DB Rabbits resulting in retinal NV and increased vascular tortuosity as early as 4 weeks post injection. Leakage of retinal vessels developed in ~80% of animals by Week 6 which peaked in area and intensity by Week 14. NV was always towards the cone dense region bellow the optic nerve head and these areas exhibited the earliest signs of leakage, though leakage superior to the ONH was common several weeks later. Vascular dilation was apparent with FA and OCT. Leakage was not detectable using ICG angiography either due to background signal from the choroid or the lack of dye accumulation. Treatment with Avastin suppressed retinal leakage and vessel dilation by Day 3. Pathology returned within 5 weeks post Avastin treatment in some animals and by Week 9 all animals had returned to pre-Avastin pathology.

Conclusions : DL-AAA induced NV, retinal vascular leakage, and vessel dilation in all eyes of DB rabbits. The pathology required 10-14 weeks to fully develop after DL-AAA administration and remained stable without additional induction article required. Treatment with the anti-VEGF Avastin, suppressed vascular leakage for a period of time which returned as the drug was reduced to non-therapeutics levels (4-8 weeks). After wash out, the retina returned to baseline leakage. A single intravitreal injection of DL-AAA results in an unique model of chronic retinal vascular leakage similar to wet AMD which can be suppressed by anti-VEGF therapies and may be used to evaluate other therapeutic targets and sustained release devices.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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