Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Princess Alexandra Eye Pavilion, NHS Lothian, Edinburgh, Scotland, United Kingdom.
Invest Ophthalmol Vis Sci. 2023 Dec 1;64(15):33. doi: 10.1167/iovs.64.15.33.
Genome editing is an emerging group of technologies with the potential to ameliorate dominant, monogenic human diseases such as late-onset retinal degeneration (L-ORD). The goal of this study was to identify disease stages and retinal locations optimal for evaluating the efficacy of a future genome editing trial.
Twenty five L-ORD patients (age range, 33-77 years; median age, 59 years) harboring the founder variant S163R in C1QTNF5 were enrolled from three centers in the United Kingdom and United States. Patients were examined with widefield optical coherence tomography (OCT) and chromatic perimetry under dark-adapted and light-adapted conditions to derive phenomaps of retinal disease. Results were analyzed with a model of a shared natural history of a single delayed exponential across all subjects and all retinal locations.
Critical age for the initiation of photoreceptor loss ranged from 48 years at the temporal paramacular retina to 74 years at the inferior midperipheral retina. Subretinal deposits (sRET-Ds) became more prevalent as critical age was approached. Subretinal pigment epithelial deposits (sRPE-Ds) were detectable in the youngest patients showing no other structural or functional abnormalities at the retina. The sRPE-D thickness continuously increased, reaching 25 µm in the extrafoveal retina and 19 µm in the fovea at critical age. Loss of light sensitivity preceded shortening of outer segments and loss of photoreceptors by more than a decade.
Retinal regions providing an ideal treatment window exist across all severity stages of L-ORD.
基因组编辑是一组新兴技术，具有改善显性单基因人类疾病（如晚期视网膜变性（L-ORD）的潜力。本研究的目的是确定疾病阶段和视网膜位置，以评估未来基因组编辑试验的疗效。
从英国和美国的三个中心招募了 25 名携带 C1QTNF5 中的 S163R 创始人变体的 L-ORD 患者（年龄范围 33-77 岁；中位年龄 59 岁）。对患者进行广角光学相干断层扫描（OCT）和暗适应和明适应下的色觉视野检查，以获得视网膜疾病的表型图。结果通过对所有受试者和所有视网膜位置的单个延迟指数的共享自然史的模型进行分析。
感光细胞丧失的起始关键年龄从颞侧旁中心视网膜的 48 岁到下周边中部视网膜的 74 岁不等。随着关键年龄的临近，视网膜下沉积物（sRET-Ds）变得更加普遍。在最早出现其他结构或功能异常的患者中可以检测到视网膜下色素上皮沉积物（sRPE-Ds）。sRPE-D 的厚度不断增加，在黄斑区外达到 25 µm，在黄斑区达到 19 µm。光敏感度丧失早于外节缩短和感光细胞丧失超过十年。
在 L-ORD 的所有严重程度阶段都存在提供理想治疗窗口的视网膜区域。
Zotero 插件
