July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Characterization of DL-2-aminoadipic acid-induced histopathological changes in nonhuman primate retina
Author Affiliations & Notes
  • Shervin Liddie
    RxGen Inc., New Haven, Connecticut, United States
  • Chintan Patel
    RxGen Inc., New Haven, Connecticut, United States
  • Wenzheng Hu
    RxGen Inc., New Haven, Connecticut, United States
  • Robin J Goody
    RxGen Inc., New Haven, Connecticut, United States
  • Matthew S Lawrence
    RxGen Inc., New Haven, Connecticut, United States
  • Footnotes
    Commercial Relationships   Shervin Liddie, None; Chintan Patel, None; Wenzheng Hu, None; Robin Goody, None; Matthew Lawrence, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5993. doi:
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      Shervin Liddie, Chintan Patel, Wenzheng Hu, Robin J Goody, Matthew S Lawrence; Characterization of DL-2-aminoadipic acid-induced histopathological changes in nonhuman primate retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5993.

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

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Purpose : We have previously described the longitudinal in vivo imaging of the chronic vascular leakage and retinal pathology induced by the intravitreal (IVT) administration of DL-2-aminoadipic acid (DLAAA) in nonhuman primates. To further characterize DLAAA pathophysiology we have extended our analyses to the histopathological and immunohistochemical (IHC) assessment of DLAAA induced retinal degeneration to further establish relevance to human disease.

Methods : Eyes of adult African green monkeys (Chlorocebus sabaeus, St. Kitts origin) received intravitreal injections of DLAAA (5 mg/200µL). Animals were euthanized and eyes collected 12-18 weeks later. Globes were fixed in Davidson’s fixative for 24 hours followed by transfer to 10% neutral buffered formalin for hematoxylin and eosin histopathology (H&E) and IHC.

Results : IVT administration of DLAAA resulted in retinal degeneration and neovascularization. H&E evaluation of retinal sections from DLAAA retina revealed extensive haemorrhage and multifocal proliferation of tortuous, new blood vessels located below the nerve fiber layer and extending into the outer layers of the retina. Retinal degeneration was more severe in the central retina characterized by marked thinning of all layers, decreased cellularity of the inner and outer nuclear layers, photoreceptor layer and the ganglion cell layer. Neovascularization was evident by H&E and confirmed by IHC staining of the proliferative endothelial cells for von-Willebrand Factor. Glial fibrillary acidic protein (GFAP) staining revealed evidence of reactive gliosis throughout the peripheral retina and near absence of GFAP-positive glial cells in the central retina, which was consistent with the observed central retinal degeneration.

Conclusions : The study highlighted significant DLAAA-induced histological changes including evidence of retinal degeneration and loss of cells across all layers of the retina, which was associated with increased reactive gliosis and intraretinal neovascularization. DLAAA-induced retinal pathology in the nonhuman primate provides a model to quantitatively evaluate response to intervention with agents targeting retinal neovascular and degenerative pathways by both in vivo imaging and histopathology.

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


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