Description of a Nonhuman Primate Model of Retinal Ischemia/Reperfusion Injury

PURPOSE: To establish an inducible model of retinal ischemia/reperfusion injury (RI/RI) in nonhuman primates (NHPs) to improve our understanding of the disease conditions and evaluate treatment interventions in humans. METHODS: We cannulated the right eye of rhesus macaques with a needle attached to a normal saline solution reservoir at up to 1.9 m above the eye level that resulted in high intraocular pressure of over 100 mm Hg for 90 minutes. Retinal morphology and function were monitored before and after RI/RI over two months by fundus photography, optical coherence tomography, electroretinography, and visual evoked potential. Terminal experiments involved immunostaining for retinal ganglion cell marker Brn3a, glial fibrillary acidic protein, and quantitative polymerase chain reaction to assess retinal inflammatory biomarkers. RESULTS: We observed significant and progressive declines in retinal and retinal nerve fiber layer thickness in the affected eye after RI/RI. We noted significant reductions in amplitudes of electroretinography a-wave, b-wave, and visual evoked potential N2-P2, with minimal recovery at 63 days after injury. Terminal experiments conducted two months after injury revealed ∼73% loss of retinal ganglion cells and a fivefold increase in glial fibrillary acid protein immunofluorescence intensity compared to the uninjured eyes. We observed marked increases in tumor necrosis factor–alpha, interferon-gamma, interleukin-1beta, and inducible nitric oxide synthase in the injured retinas. CONCLUSIONS: The results demonstrated that the pathophysiology observed in the NHP model of RI/RI is comparable to that of human diseases and suggest that the NHP model may serve as a valuable tool for translating interventions into viable treatment approaches. TRANSLATIONAL RELEVANCE: The model serves as a useful platform to study potential interventions and treatments for RI/RI or blinding retinal diseases.