Walters Sarah, Schwarz Christina, Sharma Robin, Rossi Ethan A, Fischer William S, DiLoreto David A, Strazzeri Jennifer, Nelidova Dasha, Roska Botond, Hunter Jennifer J, Williams David R, Merigan William H
The Institute of Optics, University of Rochester, Rochester, NY, USA.
Center for Visual Science, University of Rochester, Rochester, NY, USA.
Biomed Opt Express. 2018 Dec 5;10(1):66-82. doi: 10.1364/BOE.10.000066. eCollection 2019 Jan 1.
Progress is needed in developing animal models of photoreceptor degeneration and evaluating such models with longitudinal, noninvasive techniques. We employ confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT) and high-resolution retinal imaging to noninvasively observe the retina of non-human primates with induced photoreceptor degeneration. Photoreceptors were imaged at the single-cell scale in three modalities of adaptive optics scanning light ophthalmoscopy: traditional confocal reflectance, indicative of waveguiding; a non-confocal offset aperture technique visualizing scattered light; and two-photon excited fluorescence, the time-varying signal of which, at 730 nm excitation, is representative of visual cycle function. Assessment of photoreceptor structure and function using these imaging modalities revealed a reduction in retinoid production in cone photoreceptor outer segments while inner segments appeared to remain present. Histology of one retina confirmed loss of outer segments and the presence of intact inner segments. This unique combination of imaging modalities can provide essential, clinically-relevant information on both the structural integrity and function of photoreceptors to not only validate models of photoreceptor degeneration but potentially evaluate the efficacy of future cell and gene-based therapies for vision restoration.
在开发光感受器退化的动物模型以及使用纵向、非侵入性技术评估此类模型方面需要取得进展。我们采用共聚焦扫描激光眼科显微镜、光学相干断层扫描（OCT）和高分辨率视网膜成像技术，对诱导光感受器退化的非人灵长类动物的视网膜进行非侵入性观察。在自适应光学扫描激光眼科显微镜的三种模式下，以单细胞尺度对光感受器进行成像：传统共聚焦反射，指示波导；一种可视化散射光的非共聚焦偏移孔径技术；以及双光子激发荧光，其在730nm激发下的时变信号代表视觉循环功能。使用这些成像模式对光感受器结构和功能的评估显示，视锥光感受器外段的视黄醛生成减少，而内段似乎仍然存在。一只视网膜的组织学检查证实外段缺失且内段完整。这种独特的成像模式组合可以提供关于光感受器结构完整性和功能的重要、临床相关信息，不仅可以验证光感受器退化模型，还可能评估未来基于细胞和基因的视力恢复疗法的疗效。
