Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium

被引:11
作者
Bennis, Anna [1 ,2 ]
ten Brink, Jacoline B. [1 ]
Moerland, Perry D. [3 ]
Heine, Vivi M. [4 ,5 ]
Bergen, Arthur A. [1 ,2 ,6 ]
机构
[1] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands
[2] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci NIN KNAW, Amsterdam, Netherlands
[3] Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Bioinformat Lab, Amsterdam, Netherlands
[4] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Child Neurol, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
[5] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
[6] Acad Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands
关键词
ROD OUTER SEGMENTS; STEM-CELLS; MACULAR DEGENERATION; FUNCTIONAL-NEURONS; OXIDATIVE STRESS; MOUSE; PHAGOCYTOSIS; TRANSPLANTATION; FIBROBLASTS; ACTIVATION;
D O I
10.1371/journal.pone.0182983
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background The retinal pigment epithelium (RPE) is a neural monolayer lining the back of the eye. Degeneration of the RPE leads to severe vision loss in, so far incurable, diseases such as age-related macular degeneration and some forms of retinitis pigmentosa. A promising future replacement therapy may be autologous iris epithelial cell transdifferentiation into RPE in vitro and, subsequently, transplantation. In this study we compared the gene expression profiles of the iris epithelium (IE) and the RPE. Methods We collected both primary RPE- and IE cells from 5 freshly frozen human donor eyes, using respectively laser dissection microscopy and excision. We performed whole-genome expression profiling using 44k Agilent human microarrays. We investigated the gene expression profiles on both gene and functional network level, using R and the knowledge database Ingenuity. Results The major molecular pathways related to the RPE and IE were quite similar and yielded basic neuro-epithelial cell functions. Nonetheless, we also found major specific differences: For example, genes and molecular pathways, related to the visual cycle and retinol biosynthesis are significantly higher expressed in the RPE than in the IE. Interestingly, Wnt and aryl hydrocarbon receptor (AhR-) signaling pathways are much higher expressed in the IE than in the RPE, suggesting, respectively, a possible pluripotent and high detoxification state of the IE. Conclusions This study provides a valuation of the similarities and differences between the expression profiles of the RPE and IE. Our data combined with that of the literature, represent a most comprehensive perspective on transcriptional variation, which may support future research in the development of therapeutic transplantation of IE.
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页数:18
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