PDF(Pubmed)
Abstract：
Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.
摘要：
视网膜变性的动物模型对于了解疾病和测试潜在的疗法至关重要。诱导变性通常涉及通过破坏代谢途径杀死光感受器的化学物质的施用，信号通路，或蛋白质合成。虽然化学诱导的变性已经在各种动物(小鼠，老鼠,兔子,猫科动物,13衬松鼠(13-LGS),猪,小鸡)，很少有研究使用非侵入性高分辨率视网膜成像来监测体内细胞效应。这里,我们使用纵向扫描光检眼镜（SLO），光学相干层析成像，和自适应光学SLO成像，锥形优势13-LGS(46只动物，52只眼）以检查玻璃体内注射化学物质后的视网膜结构，以前被证明会引起光感受器变性，在2019年和2020年的活跃季节。我们发现碘乙酸引起严重的全视网膜损伤，除了一只眼睛，其接收的浓度最低。虽然硝普钠成功地诱导了视网膜外层的变性，结果是可变的，并且在50％的对侧对照眼中也观察到损伤。三磷酸腺苷和衣霉素诱导的视网膜外特异性损伤具有不同的结果，而注射thapsigargin的眼睛没有退化的迹象。鉴于我们观察到的损伤的可变性，检查这种变异性可能的生理来源的后续研究至关重要.这些额外的研究应进一步推进化学诱导的光感受器变性模型在视锥占优势的13-LGS中的应用。
