Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA; Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211, USA.
Exp Eye Res. 2013 Nov;116:402-10. doi: 10.1016/j.exer.2013.10.006. Epub 2013 Oct 14.
Late-infantile neuronal ceroid lipofuscinosis (CLN2) is a hereditary neurological disorder characterized by progressive retinal degeneration and vision loss, cognitive and motor decline, seizures, and pronounced brain atrophy. The progressive loss of neurological functions eventually leads to death, usually by the early teenage years. Utilizing a canine model of CLN2, therapeutic studies to inhibit the brain and retinal degenerations are currently under way. Using this dog model, studies were undertaken to compare quantitative assessments of the pupillary light reflex (PLR) and electroretinography (ERG) as tools for evaluating the effects of the disease on retinal function. The PLR and ERG were recorded in normal and CLN2-affected Dachshunds at 2 month intervals between the ages of 4 and 10 months. Using custom instrumentation for quantitative PLR assessments, a series of white light stimuli of varying intensity was used to elicit pupil constriction, and pupil images were recorded using continuous infrared illumination and an infrared-sensitive camera. Electroretinography was used to evaluate retinal function in the same dogs. As the disease progressed, affected dogs exhibited progressive and profound declines in ERG amplitudes under both scotopic and photopic conditions. With low intensity light stimuli, CLN2 was also accompanied by progressive deficits in the PLR. Changes in the PLR to dim light stimuli included significant deficits in latency, constriction velocity, constriction amplitude, and redilation velocity. However, despite the almost complete loss of detectable ERG responses by disease end stage, the PLR to bright stimuli was well preserved throughout the disease progression. These findings demonstrate that the PLR is much more sensitive than the ERG in detecting residual retinal function in animal models of retinal degenerative disease. The preservation of the PLR in dogs with profoundly depressed ERGs correlates with a preservation of visually-mediated behavior even late in the disease progression. Quantitative analysis of the PLR has potential as a biomarker in animal models of retinal degenerative diseases and in evaluating the efficacy of therapeutic interventions in preserving retinal function.
晚发性神经元蜡样脂褐质沉积症（CLN2）是一种遗传性神经疾病，其特征为进行性视网膜变性和视力丧失、认知和运动能力下降、癫痫发作以及明显的脑萎缩。神经功能的逐渐丧失最终导致死亡，通常在青少年早期。目前正在利用 CLN2 的犬模型进行抑制脑和视网膜变性的治疗研究。利用这种犬模型，进行了研究以比较瞳孔光反射（PLR）和视网膜电图（ERG）的定量评估，作为评估疾病对视网膜功能影响的工具。在 4 至 10 个月之间，以 2 个月为间隔，在正常和受 CLN2 影响的达克斯猎犬中记录 PLR 和 ERG。使用用于定量 PLR 评估的定制仪器，使用一系列不同强度的白光刺激来引发瞳孔收缩，并使用连续的红外照明和红外敏感相机记录瞳孔图像。在同一批狗中使用视网膜电图评估视网膜功能。随着疾病的进展，受影响的狗在暗适应和明适应条件下表现出 ERG 幅度的进行性和深刻下降。在低强度光刺激下，CLN2 还伴有 PLR 的进行性缺陷。对弱光刺激的 PLR 变化包括潜伏期、收缩速度、收缩幅度和再扩张速度的显著缺陷。然而，尽管在疾病末期几乎完全丧失了可检测的 ERG 反应，但在整个疾病进展过程中，对强光刺激的 PLR 仍保持良好。这些发现表明，PLR 在检测视网膜退行性疾病动物模型中的残留视网膜功能方面比 ERG 更敏感。在 ERG 明显降低的狗中，PLR 的保留与即使在疾病进展的晚期，仍能保持视觉介导的行为相关。PLR 的定量分析有可能成为视网膜退行性疾病动物模型中的生物标志物，并评估治疗干预保留视网膜功能的疗效。
