Gendron Robert L, Good William V, Miskiewicz Ewa, Tucker Stephanie, Phelps Dale L, Paradis Helene
Division of Basic Medical Sciences, Department of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Mol Vis. 2006 Feb 22;12:108-16.
Identification of unique proteins involved in retinopathy of prematurity (ROP) may facilitate new and more effective diagnostic tools and molecular-based treatments for ROP. Tubedown-1 (Tbdn-1), a novel homeostatic protein which copurifies with an acetyltransferase activity, is expressed in normal retinal endothelium and is specifically suppressed in retinal endothelial cells from patients with proliferative diabetic retinopathy. Furthermore, recent in vivo knockdown studies in mice have revealed that Tbdn-1 is important for retinal blood vessel homeostasis and for preventing retinal neovascularization in adults. The purpose of the present study was to determine if the expression pattern of Tbdn-1 is altered during oxygen-induced retinal neovascularization in mice and in a specimen of stage 3 human ROP.
Specimens of oxygen-induced retinal neovascularization in mice, and a single specimen of active stage 3 ROP were studied by immunohistochemistry and digital image analysis using antibodies raised against Tbdn-1 and other blood vessel markers.
The pattern of Tbdn-1 expression during the course of oxygen-induced retinal neovascularization in mice suggests a regulating role in neonatal retinopathy. Retinal lesions from oxygen-induced retinal neovascularization in mice display suppression of retinal endothelial Tbdn-1 protein expression in conjunction with an increase in expression of proliferating cell nuclear antigen (a marker of proliferation) and alpha smooth muscle actin (a marker of myofibroblastic cells). Abnormal blood vessels within vitreoretinal neovascular lesions in a human specimen of active stage 3 ROP did not show Tbdn-1 protein expression.
These results suggest that the loss of retinal endothelial Tbdn-1 expression may be a contributing factor in retinal blood vessel proliferation in ROP.
鉴定早产儿视网膜病变（ROP）中涉及的独特蛋白质，可能有助于开发新的、更有效的ROP诊断工具和基于分子的治疗方法。Tubedown-1（Tbdn-1）是一种与乙酰转移酶活性共纯化的新型稳态蛋白，在正常视网膜内皮中表达，在增殖性糖尿病视网膜病变患者的视网膜内皮细胞中被特异性抑制。此外，最近在小鼠体内进行的敲低研究表明，Tbdn-1对视网膜血管稳态以及预防成年小鼠视网膜新生血管形成很重要。本研究的目的是确定在小鼠氧诱导性视网膜新生血管形成过程中以及在3期人类ROP标本中，Tbdn-1的表达模式是否发生改变。
通过免疫组织化学和数字图像分析，使用针对Tbdn-1和其他血管标志物产生的抗体，研究小鼠氧诱导性视网膜新生血管形成的标本以及1例活跃期3期ROP的单个标本。
小鼠氧诱导性视网膜新生血管形成过程中Tbdn-1的表达模式表明其在新生儿视网膜病变中起调节作用。小鼠氧诱导性视网膜新生血管形成的视网膜病变显示视网膜内皮Tbdn-1蛋白表达受到抑制，同时增殖细胞核抗原（增殖标志物）和α平滑肌肌动蛋白（肌成纤维细胞标志物）的表达增加。在1例活跃期3期ROP人类标本的玻璃体视网膜新生血管病变中的异常血管未显示Tbdn-1蛋白表达。
这些结果表明，视网膜内皮Tbdn-1表达的丧失可能是ROP中视网膜血管增殖的一个促成因素。
