Uren Philip J, Lee Justine T, Doroudchi M Mehdi, Smith Andrew D, Horsager Alan
Molecular and Computational Biology, University of Southern California, Los Angeles, CA.
Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Mol Vis. 2014 Nov 14;20:1612-28. eCollection 2014.
Retinitis pigmentosa (RP) is a photoreceptor disease that affects approximately 100,000 people in the United States. Treatment options are limited, and the prognosis for most patients is progressive vision loss. Unfortunately, understanding of the molecular underpinnings of RP initiation and progression is still limited. However, the development of animal models of RP, coupled with high-throughput sequencing, has provided an opportunity to study the underlying cellular and molecular changes in this disease.
Using RNA-Seq, we present the first retinal transcriptome analysis of the rd10 murine model of retinal degeneration.
Our data confirm the loss of rod-specific transcripts and the increased relative expression of Müller-specific transcripts, emphasizing the important role of reactive gliosis and innate immune activation in RP. Moreover, we report substantial changes in relative isoform usage among neuronal differentiation and morphogenesis genes, including a marked shift to shorter transcripts.
Our analyses implicate remodeling of the inner retina and possible Müller cell dedifferentiation.
视网膜色素变性（RP）是一种光感受器疾病，在美国约有10万人受其影响。治疗选择有限，大多数患者的预后是渐进性视力丧失。不幸的是，对RP发病和进展的分子基础的了解仍然有限。然而，RP动物模型的发展，结合高通量测序，为研究该疾病潜在的细胞和分子变化提供了机会。
我们使用RNA测序技术，首次对视网膜变性的rd10小鼠模型进行了视网膜转录组分析。
我们的数据证实了视杆细胞特异性转录本的丢失以及穆勒细胞特异性转录本相对表达的增加，强调了反应性胶质增生和先天免疫激活在RP中的重要作用。此外，我们报告了神经元分化和形态发生基因中相对异构体使用的显著变化，包括明显向较短转录本的转变。
我们的分析表明视网膜内层发生重塑，穆勒细胞可能发生去分化。
