Primate model of chronic retinal neovascularization and vascular leakage
| Autor: | Donnicia James, Anish Kurian, Chintan Patel, Lori-Ann Christie, Thomas C. Hohman, Wenzheng Hu, Matthew S Lawrence, Richard Torres, Robin J Goody |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Retinal degeneration Male medicine.medical_specialty genetic structures Fundus Oculi Retinal Neovascularization Article Neovascularization 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Ophthalmology Chlorocebus aethiops medicine Animals Fluorescein Angiography Macular telangiectasia Aflibercept medicine.diagnostic_test business.industry Vascular disease Retinal Vessels Retinal Diabetic retinopathy medicine.disease Fluorescein angiography Sensory Systems eye diseases Disease Models Animal 030104 developmental biology chemistry Chronic Disease 030221 ophthalmology & optometry Female sense organs medicine.symptom business Tomography Optical Coherence medicine.drug |
| Zdroj: | Exp Eye Res |
| Popis: | The purpose of this study was to characterize and develop a primate model of chronic retinal neovascularization and vascular leakage that can be employed to assess efficacy of experimental therapeutics targeting retinal ischemic and neovascular diseases. African green monkeys received bilateral intravitreal (IVT) injection of DL-alpha-aminoadipic acid (DLAAA; 5 mg) following ophthalmic examination, color fundus photography, fluorescein angiography (FA) and optical coherence tomography (OCT). Imaging was repeated to evaluate progression and subsequent stabilization of retinal vascular pathology elicited by DLAAA. Aflibercept (Eylea) was administered IVT (1.4 mg) to assess effects on vascular leakage. Ocular tissue was collected for histopathology and glial fibrillary acidic protein (GFAP), von Willebrand Factor (vWF), CD105/endoglin, VEGF and CD68 immunohistochemistry to study retinal degeneration and vascular remodeling. IVT DLAAA administration resulted in telangiectatic vessel formation as early as two-weeks post-injection, followed by retinal vascular leakage and inner retinal edema. Neovascular lesion progression was evident up to 8–10 weeks post-injection before stabilizing into a vascular leakage state that persisted beyond 90 weeks. Histopathology and immunostaining revealed retinal degeneration and neovascularization, increased expression of vWF, CD105/endoglin, VEGF and CD68 immunoreactivities in addition to Muller cell loss. Aflibercept significantly attenuated vascular leakage for 2–4 weeks before progressive return of leakage from weeks 4–8. Lesions remained responsive to anti-VEGF administration at 90 weeks after DLAAA injection. Findings support application of the primate DLAAA-induced retinal vascular leakage model for efficacy evaluations of candidate therapeutics and sustained release strategies targeting exudative AMD, diabetic retinopathy, macular telangiectasia and other retinal ischemic and neovascular diseases. Findings confirm relevance of the DLAAA primate phenotype to understanding shared retinal vascular disease mechanisms and macular susceptibility to vascular and metabolic insults. |
| Databáze: | OpenAIRE |
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