Pearl Jocelynn R, Heath Laura M, Bergey Dani E, Kelly John P, Smith Corrie, Laurino Mercy Y, Weiss Avery, Price Nathan D, LaSpada Albert, Bird Thomas D, Jayadev Suman
Institute for Systems Biology, Seattle, WA, USA.
Molecular & Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA.
J Huntingtons Dis. 2017;6(3):237-247. doi: 10.3233/JHD-170255.
Huntington's disease (HD) is a fatal progressive neurodegenerative disease characterized by chorea, cognitive impairment and psychiatric symptoms. Retinal examination of HD patients as well as in HD animal models have shown evidence of retinal dysfunction. However, a detailed retinal study employing clinically available measurement tools has not been reported to date in HD.
The goal of this study was to assess retinal responses measured by electroretinogram (ERG) between HD patients and controls and evaluate any correlation between ERG measurements and stage of disease.
Eighteen patients and 10 controls with inclusion criteria of ages 18-70 years (average age HD subjects: 52.1 yrs and control subjects: 51.9 yrs) were recruited for the study. Subjects with previous history of retinal or ophthalmologic disease were excluded. Retinal function was examined by full-field ERG in both eyes of each subject. Amplitudes and latencies to increasing flash intensities in both light- and dark-adaptation were measured in all subjects. Statistical analyses employed generalized estimating equations, which account for repeated measures per subject.
We analyzed the b-wave amplitudes of ERG response in all flash intensities and with 30 Hz flicker stimulation. We found statistically significant increased amplitudes in HD patients compared to controls at light-adapted (photopic) 24.2 and 60.9 cd.sec/m2 intensities, dark-adapted (scotopic, red flash) 0.22 cd.sec/m2 intensity, and a trend toward significance at light-adapted 30 Hz flicker. Furthermore, we found a significant increase in light-adapted ERG response from female compared to male HD patients, but no significant difference between gender amongst controls. We also noted a positive association between number of CAG repeats and ERG response at the smallest light adapted intensity (3.1 cd.sec/m2).
ERG studies revealed significantly altered retinal responses at multiple flash intensities in subjects with an HD expansion allele compared to controls. Significant differences were observed with either light-adapted tests or the dark-adapted red flash which suggests that the enhanced responses in HD patients is specific to the cone photoreceptor pathway.
亨廷顿舞蹈症（HD）是一种致命的进行性神经退行性疾病，其特征为舞蹈症、认知障碍和精神症状。对HD患者以及HD动物模型的视网膜检查已显示出视网膜功能障碍的证据。然而，迄今为止尚未有关于使用临床可用测量工具对HD进行详细视网膜研究的报道。
本研究的目的是评估HD患者与对照组之间通过视网膜电图（ERG）测量的视网膜反应，并评估ERG测量值与疾病阶段之间的任何相关性。
招募了18名患者和10名对照，纳入标准为年龄在18 - 70岁之间（HD受试者平均年龄：52.1岁，对照受试者平均年龄：51.9岁）。排除有视网膜或眼科疾病既往史的受试者。对每个受试者的双眼进行全视野ERG检查视网膜功能。在所有受试者中测量了光适应和暗适应状态下随着闪光强度增加的振幅和潜伏期。统计分析采用广义估计方程，该方程考虑了每个受试者的重复测量。
我们分析了所有闪光强度以及30Hz闪烁刺激下ERG反应的b波振幅。我们发现，与对照组相比，HD患者在光适应（明视）24.2和60.9 cd.sec/m²强度、暗适应（暗视，红色闪光）0.22 cd.sec/m²强度下的振幅有统计学显著增加，在光适应30Hz闪烁时有显著趋势。此外，我们发现与男性HD患者相比，女性HD患者的光适应ERG反应显著增加，但对照组中性别之间无显著差异。我们还注意到CAG重复次数与最小光适应强度（3.1 cd.sec/m²）下的ERG反应呈正相关。
ERG研究显示，与对照组相比，具有HD扩展等位基因的受试者在多个闪光强度下视网膜反应有显著改变。在光适应测试或暗适应红色闪光中均观察到显著差异，这表明HD患者增强的反应特定于视锥光感受器通路。
