Lewin Alfred S, Smith W Clay
Departments of Molecular Genetics and Microbiology and Ophthalmology, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Cold Spring Harb Perspect Med. 2022 Aug 8;12(9). doi: 10.1101/cshperspect.a041283.
Mutations in , the gene for rhodopsin, account for a large fraction of autosomal-dominant retinitis pigmentosa (adRP). Patients fall into two clinical classes, those with early onset, pan retinal photoreceptor degeneration, and those who experience slowly progressive disease. The latter class of patients are candidates for photoreceptor-directed gene therapy, while former may be candidates for delivery of light-responsive proteins to interneurons or retinal ganglion cells. Gene therapy for adRP may be targeted to the mutant gene at the DNA or RNA level, while other therapies preserve the viability of photoreceptors without addressing the underlying mutation. Correcting the gene and replacing the mutant RNA show promise in animal models, while sustaining viable photoreceptors has the potential to delay the loss of central vision and may preserve photoreceptors for gene-directed treatments.
视紫红质基因（rhodopsin）的突变在常染色体显性视网膜色素变性（adRP）中占很大比例。患者分为两类临床类型，一类是发病早、全视网膜光感受器退化的患者，另一类是病情进展缓慢的患者。后一类患者是光感受器定向基因治疗的候选对象，而前一类患者可能是向中间神经元或视网膜神经节细胞递送光响应蛋白的候选对象。adRP的基因治疗可以在DNA或RNA水平上针对突变基因，而其他治疗方法则在不解决潜在突变的情况下维持光感受器的活力。在动物模型中，纠正视紫红质基因并替换突变RNA显示出前景，而维持存活的光感受器有可能延缓中心视力的丧失，并可能为基因定向治疗保留光感受器。
