Assessing Photoreceptor Structure and Function in Normal and Diseased Retinae

抽象的。 遗传性视网膜变性在美国大约每1500人中就有1人受到影响，鉴于 极端的基因和表型异质性，治疗这些毁灭性疾病的前景是 艰巨的任务。然而，检查新的治疗策略的试验正在进行中。一个重要的 在此类试验的早期阶段成功的关键是选择合理的治疗方法 潜在性--例如，没有剩余视锥感光器的视网膜不是最好的目标 旨在恢复视锥功能的基因治疗方法。此外，目前用于评估的临床工具 视网膜结构相对不敏感和宏观，限制了监测治疗的能力 这些患者的反应。因此，需要敏感的、非侵入式的、高分辨率 评估光感受器结构的技术。先进的眼部成像计划已经取得了 这一前沿创新的自适应光学(AO)成像仪器的重大进展 用单细胞分辨率探测光感受器内外节段结构，创建软件 提取感光细胞镶嵌的定量度量，并开发工具来准确和 从光学相干层析成像(OCT)图像可靠地测量光感受器结构 视网膜。从临床角度来看，这些工具还处于相对初级阶段，因此我们建议帮助 通过以下具体目标加速翻译：1)定义残留物中的可变性 人类色盲患者的视锥细胞群(ACHM)，2)表征 L/M视蛋白突变个体的光感受器嵌合体，以及3)阐明视杆/视锥的贡献 OCT图像中的光感受器层。正在研究的特定疾病有广泛的 棒/锥参与，是当前或正在出现的治疗努力的目标，并继续代表一种 我们多学科研究团队的主要优势。预计这项工作将具有重大的积极意义 影响，这里确定的高分辨率基因型-表型关系提供了更好的 遗传性视网膜变性患者的治疗潜力以及 在新出现的临床试验中为评估光感受器结构生产经过验证的工具。我们的建议 满足NEI出版物《愿景研究：需求、差距和 机会“：”描述视网膜的黄斑和黄斑周围区域的特征，以更好地理解 倾向于黄斑疾病“和”翻译高分辨率视网膜成像技术，如 将自适应光学技术转化为具有成本效益且易于使用的平台，用于临床常规使用。

ABSTRACT . Inherited retinal degenerations affect approximately 1 in 1,500 individuals in the US, and given the extreme genotypic and phenotypic heterogeneity, the prospect of treating these devastating diseases is a formidable task. Nevertheless, trials examining novel therapeutic strategies are underway. An important key to success in the early phases of such trials is selection of patients with reasonable therapeutic potential – for example, a retina with no remaining cone photoreceptors would not be the best target for a gene therapy approach aiming to restore cone function. In addition, current clinical tools for assessing retinal structure are relatively insensitive and macroscopic, limiting the ability to monitor therapeutic response in these patients. As such, there is a need for sensitive, noninvasive, high-resolution techniques to assess photoreceptor structure. The Advanced Ocular Imaging Program has made significant advances on this front – advancing innovative adaptive-optics (AO) imaging instrumentation for probing photoreceptor inner- and outer-segment structure with single-cell resolution, creating software for extracting quantitative metrics of the photoreceptor mosaic, and developing tools for making accurate and reliable measurements of photoreceptor structure from optical coherence tomography (OCT) images of the retina. From a clinical perspective, these tools are in relative infancy, thus we propose to help accelerate their translation through the following specific aims: 1) Define the variability in the remnant cone population in human patients with achromatopsia (ACHM), 2) Characterize the integrity of the photoreceptor mosaic in individuals with L/M opsin mutations, and 3) Elucidate the rod/cone contribution to the photoreceptor layers in OCT images. The specific diseases being studied have a wide range of rod/cone involvement, are current or emerging targets for treatment efforts, and continue to represent a major strength of our multidisciplinary research team. This work is expected to have a significant positive impact, with the high-resolution genotype-phenotype relationships identified here providing a better understanding of the therapeutic potential in patients with inherited retinal degenerations as well as producing validated tools for assessing photoreceptor structure in emerging clinical trials. Our proposal addresses two emerging needs identified in the NEI Publication “Vision Research: Needs, Gaps, and Opportunities”: “Characterize the macula and perifoveal regions of the retina to better understand the predilection of the macula for disease,” and “Translate high-resolution retinal imaging technologies, like adaptive optics, into cost-effective and easy-to-use platforms for routine clinical use.”