Velez Gabriel, Mahajan Vinit B
Omics Laboratory, Stanford University, Palo Alto, CA, USA.
Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304, USA.
iScience. 2020 Oct 13;23(11):101667. doi: 10.1016/j.isci.2020.101667. eCollection 2020 Nov 20.
Rare diseases are an emerging global health priority. Although individually rare, the prevalence of rare "orphan" diseases is high, affecting approximately 300 million people worldwide. Treatments for these conditions are often inadequate, leaving the disease to progress unabated. Here, we review the clinical features and pathophysiology of neovascular inflammatory vitreoretinopathy (NIV), a rare inflammatory retinal disease caused by mutations in the gene. Although the prevalence of NIV is low (1 in 1,000,000 people), the disease mimics more common causes of blindness (e.g. uveitis, retinitis pigmentosa, proliferative diabetic retinopathy, and proliferative vitreoretinopathy) at distinct clinical stages. There is no cure for NIV to date. We highlight how personalized proteomics helped identify potential stage-specific biomarkers and drug targets in liquid vitreous biopsies. The NIV vitreous proteome revealed enrichment of molecular pathways associated with common retinal pathologies and implicated superior targets for therapeutic drug repositioning. In addition, we review our pipeline for collecting, storing, and analyzing ophthalmic surgical samples. This approach can be adapted to treat a variety of rare genetic diseases.
罕见病正成为全球新兴的卫生重点。尽管每种罕见病都很罕见，但罕见“孤儿”病的患病率却很高，全球约有3亿人受其影响。针对这些病症的治疗往往不足，导致病情持续发展。在此，我们综述了新生血管性炎性玻璃体视网膜病变（NIV）的临床特征和病理生理学，这是一种由该基因的突变引起的罕见炎性视网膜疾病。尽管NIV的患病率很低（每100万人中有1例），但在不同的临床阶段，该疾病会模仿更常见的致盲原因（如葡萄膜炎、色素性视网膜炎、增殖性糖尿病视网膜病变和增殖性玻璃体视网膜病变）。迄今为止，NIV尚无治愈方法。我们强调了个性化蛋白质组学如何有助于在液体玻璃体活检中识别潜在的阶段特异性生物标志物和药物靶点。NIV玻璃体蛋白质组揭示了与常见视网膜病变相关的分子途径的富集，并暗示了治疗药物重新定位的优越靶点。此外，我们还综述了我们收集、储存和分析眼科手术样本的流程。这种方法可适用于治疗多种罕见遗传病。
