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Abstract：
Due to improved phenotyping and genetic characterization, the field of \'incurable\' and \'blinding\' inherited retinal diseases (IRDs) has moved substantially forward. Decades of ascertainment of IRD patient data from Philadelphia and Toronto centers illustrate the progress from Mendelian genetic types to molecular diagnoses. Molecular genetics have been used not only to clarify diagnoses and to direct counseling but also to enable the first clinical trials of gene-based treatment in these diseases. An overview of the recent reports of gene augmentation clinical trials by subretinal injections is used to reflect on the reasons why there has been limited success in this early venture into therapy. These first-in human experiences have taught that there is a need for advancing the techniques of delivery of the gene products - not only for refining further subretinal trials, but also for evaluating intravitreal delivery. Candidate IRDs for intravitreal gene delivery are then suggested to illustrate some of the disorders that may be amenable to improvement of remaining central vision with the least photoreceptor trauma. A more detailed understanding of the human IRDs to be considered for therapy and the calculated potential for efficacy should be among the routine prerequisites for initiating a clinical trial.
摘要：
由于改进的表型和遗传特征，“不可治愈”和“致盲”遗传性视网膜疾病（IRD）领域已取得实质性进展。来自费城和多伦多中心的IRD患者数据的数十年确定说明了从孟德尔遗传类型到分子诊断的进展。分子遗传学不仅用于明确诊断和指导咨询，而且还用于实现这些疾病中基于基因的治疗的首次临床试验。对最近通过视网膜下注射进行基因增强临床试验的报道进行了概述，以反映为什么在这种早期疗法中取得了有限的成功。这些首次人类经历告诉我们，有必要推进基因产物的递送技术-不仅是为了进一步完善视网膜下试验，也用于评估玻璃体内分娩。然后建议用于玻璃体内基因递送的候选IRD来说明一些可能适合于以最少的光感受器创伤改善剩余中央视力的疾病。对考虑用于治疗的人IRD的更详细的理解和计算的疗效潜力应该是开始临床试验的常规先决条件之一。
