Division of Experimental Retinal Therapies, Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Sci Rep. 2017 Dec 20;7(1):17897. doi: 10.1038/s41598-017-18236-7.
Retinitis pigmentosa (RP) is a group of inherited retinal degenerations that lead to progressive vision loss. Over 200 mutations in 60 different genes have been shown to cause RP. Given the diversity of genes and mutations that cause RP, corrective gene therapy approaches currently in development may prove both time-consuming and cost-prohibitive for treatment of all forms of RP. An alternative approach is to find common biological pathways that cause retinal degeneration in various forms of RP, and identify new molecular targets. With this goal, we analyzed the retinal transcriptome of two non-allelic forms of RP in dogs, rcd1 and xlpra2, at clinically relevant advanced stages of the two diseases. Both diseases showed very similar trends in changes in gene expression compared to control normal dogs. Pathway analysis revealed upregulation of various components of the innate immune system in both diseases, including inflammasome and complement pathways. Our results show that the retinal transcriptome at advanced stages of RP is very similar to that of other retinal degenerative diseases such as age-related macular degeneration and diabetic retinopathy. Thus, drugs and therapeutics already in development for targeting these retinopathies may also prove useful for the treatment of many forms of RP.
色素性视网膜炎（RP）是一组遗传性视网膜变性疾病，导致进行性视力丧失。超过 200 种突变在 60 种不同的基因中已被证明可引起 RP。鉴于引起 RP 的基因和突变的多样性，目前正在开发的纠正基因治疗方法可能在治疗所有形式的 RP 方面既耗时又昂贵。另一种方法是找到导致各种形式 RP 视网膜变性的常见生物学途径，并确定新的分子靶点。为此，我们分析了两种犬类非等位基因形式的 RP（rcd1 和 xlpra2）的视网膜转录组，这两种疾病在临床上都处于疾病的晚期。与正常对照犬相比，这两种疾病的基因表达变化趋势非常相似。通路分析显示，两种疾病中先天免疫系统的各种成分均上调，包括炎症小体和补体途径。我们的结果表明，RP 晚期的视网膜转录组与其他视网膜变性疾病（如年龄相关性黄斑变性和糖尿病性视网膜病变）非常相似。因此，针对这些视网膜病变开发的药物和疗法可能对治疗许多形式的 RP 也很有用。
