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Laura Belen, Kortni Violette, Christopher Schillo, Christopher Gallotta, Christian Grant, Leslie Jost, David Hollander, Andy Whitlock; Establishing a Colony of Non-human Primates with Cystoid Macular Edema. Invest. Ophthalmol. Vis. Sci. 2018;59(9):391.
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© ARVO (1962-2015); The Authors (2016-present)
To date, there are no reliable models that accurately reproduce the disease traits of chronic vascular leakage or edema associated with retinal disorders such as Cystoid Macular Edema (CME), wet AMD, or diabetic macular edema. Such a model would be invaluable in assessing efficacy and duration of action of new treatments for retinal vascular disease. This abstract describes development of a novel model of chronic CME in a non-human primate (NHP), cynomologus macaque, by utilizing intravitreal injection of the glutamine synthase inhibitor DL-2-Aminoadipic acid (DLAAA).
Non-naïve cynomologus NHPs received intravitreal (IVT) injection of DLAAA (2.5-5mg) in one eye. Animals underwent baseline and weekly optical coherence tomography (OCT) and fluorescein angiography (FA) until sufficient disease phenotype became established. This included (but was not limited to) intra-retinal cysts, macular edema, and vascular leakage. Once the disease state plateaued, vascular endothelial growth factor (VEGF) inhibitor was administered to assess whether the induced disease state was responsive to this treatment modality. Eyes were monitored via OCT and FA post treatment to follow disease.
IVT injection of DLAAA produced a prolonged and substantial retinal disease that presented most prominently via OCT with signs of macular edema and intra-retinal cysts, but with little to no uveitis thus preserving the neural retina. The edema was evident within 4 weeks and plateaued by10 weeks. Once the pathological phenotype was stable, treatment with anti-VEGF agents yielded a partial to full resolution of the disease characteristics that lasted for 4-6 weeks, followed by a recurrence of the disease state.
The results demonstrate that this model paradigm can be used to establish sustained macular edema pathology in a non-human primate that is not associated with uveitis, preserved the neural retina, and is responsive to current standards of care. This model will allow us to create a stable colony of animals with CME that can be used as an essential tool for testing the efficacy of novel therapeutics designed to treat retina diseases associated with vascular leakage including CME, wet-AMD, and diabetic macular edema.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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