title: Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration.
abstract: BACKGROUND
  The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new therapeutics. This requires further in-depth knowledge of the similarities and differences between mouse and human RPE.
  
  
  METHODS
  We performed a microarray study to identify and functionally annotate RPE specific gene expression in mouse and human RPE. We used a meticulous method to determine C57BL/6J mouse RPE signature genes, correcting for possible RNA contamination from its adjacent layers: the choroid and the photoreceptors. We compared the signature genes, gene expression profiles and functional annotations of the mouse and human RPE.
  
  
  RESULTS
  We defined sets of mouse (64), human (171) and mouse-human interspecies (22) RPE signature genes. Not unexpectedly, our gene expression analysis and comparative functional annotation suggested that, in general, the mouse and human RPE are very similar. For example, we found similarities for general features, like "organ development" and "disorders related to neurological tissue". However, detailed analysis of the molecular pathways and networks associated with RPE functions, suggested also multiple species-specific differences, some of which may be relevant for the development of AMD. For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE. Furthermore, functions assigned to mouse and human RPE expression profiles indicate (patho-) biological differences related to AMD, such as oxidative stress, Bruch's membrane, immune-regulation and outer blood retina barrier.
  
  
  CONCLUSIONS
  These differences may be important for the development of new therapeutic strategies and translational studies in age-related macular degeneration.
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands; The Netherlands Institute for Neuroscience (NIN-KNAW), Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Bennis
authors.affiliation: The Netherlands Institute for Neuroscience (NIN-KNAW), Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; University Eye Clinic Maastricht, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Theo G M F
authors.initials: TG
authors.lastname: Gorgels
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jacoline B
authors.initials: JB
authors.lastname: Ten Brink
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
authors.affiliation: Laboratory for Neuroregeneration, the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Bossers
authors.affiliation: Department of Pediatrics / Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Vivi M
authors.initials: VM
authors.lastname: Heine
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands; The Netherlands Institute for Neuroscience (NIN-KNAW), Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Ophthalmology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Bergen
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D013045:Species Specificity; D059467:Transcriptome