PriMed Non-human Primate Research Center of Sichuan PriMed Shines Bio-tech Co., Ltd., Ya'an, Sichuan Province, China.
Eye and Vision Research Institute at New York Eye and Ear Infirmary of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Transl Vis Sci Technol. 2023 Jun 1;12(6):14. doi: 10.1167/tvst.12.6.14.
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.
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.
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.
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.
The model serves as a useful platform to study potential interventions and treatments for RI/RI or blinding retinal diseases.
建立灵长类动物（NHPs）视网膜缺血/再灌注损伤（RI/RI）的诱导模型，以增进我们对疾病状况的了解，并评估人类的治疗干预措施。
我们用一根连有生理盐水储液器的针给恒河猴右眼穿刺，使眼内压升高至超过 100mmHg，持续 90 分钟。在 RI/RI 前后两个月，通过眼底照相、光学相干断层扫描、视网膜电图和视觉诱发电位监测视网膜形态和功能。终末实验包括视网膜节细胞标志物 Brn3a、胶质纤维酸性蛋白的免疫染色和定量聚合酶链反应，以评估视网膜炎症生物标志物。
我们观察到 RI/RI 后受影响眼的视网膜和神经纤维层厚度明显且进行性下降。我们注意到视网膜电图 a 波、b 波和视觉诱发电位 N2-P2 的振幅显著降低，在损伤后 63 天恢复最小。损伤后两个月进行的终末实验显示，与未损伤眼相比，视网膜节细胞损失约 73%，胶质纤维酸性蛋白免疫荧光强度增加五倍。我们观察到损伤的视网膜中肿瘤坏死因子-α、干扰素-γ、白细胞介素-1β和诱导型一氧化氮合酶显著增加。
结果表明，NHPs RI/RI 模型中观察到的病理生理学与人类疾病相似，并表明 NHP 模型可能成为将干预措施转化为可行治疗方法的有价值工具。
王梦竹
