Open Access Open Badges Research article

Functional annotation of the human retinal pigment epithelium transcriptome

Judith C Booij1, Simone van Soest1, Sigrid MA Swagemakers23, Anke HW Essing1, Annemieke JMH Verkerk2, Peter J van der Spek2, Theo GMF Gorgels1 and Arthur AB Bergen14*

Author affiliations

1 Department of Molecular Ophthalmogenetics, Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, the Netherlands (NL)

2 Department of Bioinformatics, Erasmus Medical Center, 3015 GE Rotterdam, the Netherlands

3 Department of Genetics, Erasmus Medical Center, 3015 GE Rotterdam, the Netherlands

4 Department of Clinical Genetics, Academic Medical Centre Amsterdam, the Netherlands

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Citation and License

BMC Genomics 2009, 10:164  doi:10.1186/1471-2164-10-164

Published: 20 April 2009



To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years) were laser dissected and used for 22k microarray studies (Agilent technologies). Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software.


In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194) expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776) genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194) of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM) composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover.


Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the RPE, and is useful for candidate retinal disease gene identification or gene dose-dependent therapeutic studies.