Finnegan Sorcha, Robson Joanne, Hocking Paul M, Ali Manir, Inglehearn Chris F, Stitt Alan, Curry William J
Centre for Vision Sciences, Institute of Clinical Science, Queen's University of Belfast, Belfast, Northern Ireland, UK.
Mol Vis. 2010 Jan 11;16:7-17.
In our previous paper we undertook proteomic analysis of the normal developing chick retina to identify proteins that were differentially expressed during retinal development. In the present paper we use the same proteomic approach to analyze the development and onset of degeneration in the retinal dysplasia and degeneration (rdd) chick. The pathology displayed by the rdd chick resembles that observed in some of the more severe forms of human retinitis pigmentosa.
Two-dimensional gel electrophoresis (pH 4-7), gel image analysis, and mass spectrometry were used to profile the developing and degenerating retina of the rdd and wild-type (wt) chick retina.
Several proteins were identified by mass spectrometry that displayed differential expression between normal and rdd retina between embryonic day 12 (E12) and post-hatch day 1 (P1). Secernin 1 displayed the most significant variation in expression between rdd and wt retina; this may be due to differential phosphorylation in the rdd retina. Secernin 1 has dipeptidase activity and has been demonstrated to play a role in exocytosis; it has been shown to be overexpressed in certain types of cancer and has also been suggested as a potential neurotoxicologically relevant target. Its role in the retina and in particular its differential expression in the degenerate rdd retina remains unknown and will require further investigation. Other proteins that were differentially expressed in the rdd retina included valosin-containing protein, beta-synuclein, stathmin 1, nucleoside diphosphate kinase, histidine triad nucleotide-binding protein, and 40S ribosomal protein S12. These proteins are reported to be involved in several cellular processes, including the ubiquitin proteasome pathway, neuroprotection, metastatic suppression, transcriptional and translational regulation, and regulation of microtubule dynamics.
This proteomic study is the first such investigation of the rdd retina and represents a unique data set that has revealed several proteins that are differentially expressed during retinal degeneration in the rdd chick. Secernin 1 showed the most significant differences in expression during this degeneration period. Further investigation of the proteins identified may provide insight into the complex events underlying retinal degeneration in this animal model.
在我们之前的论文中，我们对正常发育的雏鸡视网膜进行了蛋白质组学分析，以鉴定在视网膜发育过程中差异表达的蛋白质。在本文中，我们使用相同的蛋白质组学方法来分析视网膜发育不良和变性（rdd）雏鸡视网膜的发育和变性起始情况。rdd雏鸡所表现出的病理学特征类似于在某些更严重形式的人类视网膜色素变性中观察到的情况。
使用二维凝胶电泳（pH 4 - 7）、凝胶图像分析和质谱法对rdd和野生型（wt）雏鸡视网膜的发育和变性视网膜进行分析。
通过质谱鉴定出几种在胚胎第12天（E12）和孵化后第1天（P1）之间正常视网膜和rdd视网膜之间表现出差异表达的蛋白质。分泌素1在rdd和wt视网膜之间的表达差异最为显著；这可能是由于rdd视网膜中的磷酸化差异所致。分泌素1具有二肽酶活性，并已被证明在胞吐作用中起作用；它已被证明在某些类型的癌症中过度表达，并且也被认为是一个潜在的与神经毒理学相关的靶点。它在视网膜中的作用，特别是在退化的rdd视网膜中的差异表达仍然未知，需要进一步研究。在rdd视网膜中差异表达的其他蛋白质包括含缬酪肽蛋白、β-突触核蛋白、1型微管相关蛋白、核苷二磷酸激酶、组氨酸三联体核苷酸结合蛋白和40S核糖体蛋白S12。据报道，这些蛋白质参与多种细胞过程，包括泛素蛋白酶体途径、神经保护、转移抑制、转录和翻译调控以及微管动力学调控。
这项蛋白质组学研究是首次对rdd视网膜进行此类研究，代表了一个独特的数据集，揭示了几种在rdd雏鸡视网膜变性过程中差异表达的蛋白质。分泌素1在这个变性期表现出最显著的表达差异。对鉴定出的蛋白质进行进一步研究可能有助于深入了解这种动物模型中视网膜变性背后的复杂事件。
