De Soma, Rabin David M, Salero Enrique, Lederman Patricia L, Temple Sally, Stern Jeffrey H
Center for Neuropharmacology and Neuroscience and Department of Ophthalmology, Albany Medical College, 42 New Scotland Avenue, Albany, NY 12208, USA.
Arch Ophthalmol. 2007 May;125(5):641-5. doi: 10.1001/archopht.125.5.641.
To examine changes in the retinal pigment epithelium (RPE) in eyes with age-related macular degeneration (AMD) and specifically to characterize alphaB-crystallin expression in RPE cells as a biomarker in this disease.
Maculae from human patients diagnosed as having AMD or from age-matched control eyes were isolated, cryosectioned, and analyzed immunohistochemically for alphaB-crystallin and for cell type-specific markers.
In eyes with dry and wet AMD, alphaB-crystallin was heterogeneously expressed by a subpopulation of RPE cells in the macular region (frequently in cells adjacent to drusen) and in areas of RPE hypertrophy associated with wet AMD. In contrast, alphaB-crystallin was not detected at significant levels in control RPE.
Accompanying the formation of drusen in early-stage and late-stage AMD, RPE cells undergo change to express alphaB-crystallin.
The detection of alphaB-crystallin in the RPE of patients with early and advanced AMD implicates this as an AMD biomarker. Sporadic expression of alphaB-crystallin by RPE cells localized adjacent to drusen in early AMD indicates that changes in the gene expression of RPE cells accompany early stages of the disease and introduces novel potential targets for AMD therapy.
研究年龄相关性黄斑变性(AMD)患者眼睛中视网膜色素上皮(RPE)的变化,特别是将RPE细胞中αB-晶状体蛋白的表达作为该疾病的生物标志物进行特征描述。
从被诊断患有AMD的人类患者或年龄匹配的对照眼中分离黄斑,进行冷冻切片,并对αB-晶状体蛋白和细胞类型特异性标志物进行免疫组织化学分析。
在干性和湿性AMD眼中,αB-晶状体蛋白在黄斑区域的一部分RPE细胞中呈异质性表达(常见于与玻璃膜疣相邻的细胞中)以及在与湿性AMD相关的RPE肥大区域中表达。相比之下,在对照RPE中未检测到显著水平的αB-晶状体蛋白。
在早期和晚期AMD中,伴随玻璃膜疣的形成,RPE细胞发生变化以表达αB-晶状体蛋白。
在早期和晚期AMD患者的RPE中检测到αB-晶状体蛋白表明其可作为AMD的生物标志物。在早期AMD中,紧邻玻璃膜疣的RPE细胞散在表达αB-晶状体蛋白,这表明RPE细胞基因表达的变化伴随着疾病的早期阶段,并为AMD治疗引入了新的潜在靶点。