Research resource: nuclear receptor atlas of human retinal pigment epithelial cells: potential relevance to age-related macular degeneration.
Retinal pigment epithelial (RPE) cells play a vital role in retinal physiology by forming the outer blood-retina barrier and supporting photoreceptor function. Retinopathies including age-related macular degeneration (AMD) involve physiological and pathological changes in the epithelium, severely impairing the retina and effecting vision. Nuclear receptors (NRs), including peroxisome proliferator-activated receptor and liver X receptor, have been identified as key regulators of physiological pathways such as lipid metabolic dysregulation and inflammation, pathways that may also be involved in development of AMD. However, the expression levels of NRs in RPE cells have yet to be systematically surveyed. Furthermore, cell culture lines are widely used to study the biology of RPE cells, without knowledge of the differences or similarities in NR expression and activity between these in vitro models and in vivo RPE. Using quantitative real-time PCR, we assessed the expression patterns of all 48 members of the NR family plus aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator in human RPE cells. We profiled freshly isolated cells from donor eyes (in vivo), a spontaneously arising human cell line (in vitro), and primary cell culture lines (in vitro) to determine the extent to which NR expression in the cultured cell lines reflects that of in vivo. To evaluate the validity of using cell culture models for investigating NR receptor biology, we determined transcriptional activity and target gene expression of several moderately and highly expressed NRs in vitro. Finally, we identified a subset of NRs that may play an important role in pathobiology of AMD.
Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA.
Mary A
MA
Dwyer
Dmitri
D
Kazmin
Peng
P
Hu
Donald P
DP
McDonnell
Goldis
G
Malek
D000367:Age Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics; D001271:Atlases as Topic; D002460:Cell Line; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism*; D014158:Transcription, Genetic
D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator
J Cell Sci. 2003 May 15;116(Pt 10):1915-23
12668724
Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E3-9
20407009
Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):359-65
17110604
Science. 2005 Apr 15;308(5720):421-4
15761121
PLoS One. 2010 Apr 23;5(4):e10329
20428236
Diabetes. 2008 Feb;57(2):332-9
18024853
J Biol Chem. 2008 May 2;283(18):11947-53
18326047
Science. 2005 Apr 15;308(5720):419-21
15761120
Invest Ophthalmol Vis Sci. 2003 Jan;44(1):50-9
12506055
Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32
15870199
Clin Chem. 2009 Apr;55(4):611-22
19246619
Science. 2005 Apr 15;308(5720):385-9
15761122
Vision Res. 2002 Feb;42(4):487-95
11853765
Mol Pharmacol. 1997 Jun;51(6):972-82
9187263
Immunity. 2009 Aug 21;31(2):245-58
19646905
Neurobiol Aging. 2006 Jul;27(7):983-93
15979212
Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1012-7
17325140
Invest Ophthalmol Vis Sci. 1977 Oct;16(10):947-62
908648
Orphanet J Rare Dis. 2007 Feb 01;2:7
17270046
Ophthalmology. 1995 Oct;102(10):1450-60
9097791
Prog Retin Eye Res. 2010 Mar;29(2):95-112
19961953
Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1542-9
20631355
J Histochem Cytochem. 1993 Feb;41(2):253-63
8419462
J Androl. 2006 May-Jun;27(3):405-13
16452526
Mol Endocrinol. 2003 Jun;17(6):985-93
12690094
Toxicol Sci. 2007 Jan;95(1):215-26
17003102
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3687-92
20133706
Cardiovasc Res. 2001 Mar;49(4):851-62
11230985
Prog Retin Eye Res. 2010 Jan;29(1):1-18
19747980
Exp Eye Res. 2008 Apr;86(4):653-60
18313050
Circ Res. 2009 Jul 2;105(1):16-24
19461048
Mol Vis. 2009 Sep 21;15:1929-38
19784391
PPAR Res. 2008;2008:389507
18288287
Curr Drug Targets Cardiovasc Haematol Disord. 2005 Oct;5(5):377-86
16248830
Science. 2001 Nov 30;294(5548):1866-70
11729302
Cell. 2006 Aug 25;126(4):789-99
16923397
J Neurochem. 2008 May;105(4):1187-97
18182060
Am J Cardiol. 2007 Dec 3;100(11 A):n20-4
18047848
J Cell Physiol. 2003 May;195(2):241-8
12652651
Arch Ophthalmol. 1999 Mar;117(3):329-39
10088810
Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2309-17
10892878
Arch Ophthalmol. 2004 Apr;122(4):598-614
15078679
Curr Eye Res. 1994 Apr;13(4):257-61
8033587
Prog Retin Eye Res. 2008 Nov;27(6):596-607
18848639
Prostaglandins Other Lipid Mediat. 2006 Sep;80(3-4):136-43
16939878
Biol Reprod. 1999 Aug;61(2):416-21
10411521
Exp Eye Res. 1996 Feb;62(2):155-69
8698076
Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2435-41
12091448
Biochem Soc Trans. 2004 Feb;32(Pt 1):92-6
14748721
BMC Womens Health. 2008 Nov 27;8:22
19038018
Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2252-9
16888236
J Lipid Res. 2009 Feb;50(2):214-24
18772483
Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3767-77
15452088
J Nutr. 2009 Jan;139(1):26-32
19056653
Invest Ophthalmol Vis Sci. 2006 Nov;47(11):5098-105
17065531
Cell. 2009 Apr 3;137(1):26-8
19345183
Invest Ophthalmol Vis Sci. 2011 Feb 22;52(2):890-903
20847119
Biochem Biophys Res Commun. 2007 Sep 21;361(2):323-8
17655826
Circulation. 2007 Nov 6;116(19):2182-90
17967777
Ophthalmic Paediatr Genet. 1990 Mar;11(1):49-59
2190134
Ophthalmology. 2003 Jun;110(6):1151-8
12799240
Photochem Photobiol. 2004 May;79(5):470-5
15191057
Nucl Recept Signal. 2003;1:e012
16604184
J Lipid Res. 2008 Dec;49(12):2535-44
18664718
Am J Ophthalmol. 2008 Apr;145(4):716-721
18226801
Science. 1989 Aug 18;245(4919):718-25
2672330
Mol Vis. 1999 Nov 03;5:27
10562651
Exp Eye Res. 2006 Sep;83(3):638-50
16682026
Mol Vis. 2008 Jan 18;14:95-104
18253093
Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4407-20
17898259
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19273-8
18048333
Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3426-34
16123448
Drugs. 2008;68(8):1029-36
18484796
Angiogenesis. 2007;10(2):119-32
17372852
Arch Ophthalmol. 1990 Aug;108(8):1163-8
2383206
J Clin Endocrinol Metab. 2010 Jun;95(6):2885-91
20371666
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14610-5
17804788
Surv Ophthalmol. 1995 Mar-Apr;39(5):367-74
7604360
Biochem J. 2005 May 1;387(Pt 3):601-8
15595924
Graefes Arch Clin Exp Ophthalmol. 2004 Aug;242(8):710-6
15309554
Ophthalmology. 2007 Feb;114(2):253-62
17270675
Am J Epidemiol. 2008 May 15;167(10):1217-25
18359774
Prog Retin Eye Res. 2000 Mar;19(2):205-21
10674708
Science. 2009 Jul 3;325(5936):100-4
19520913
Physiol Rev. 2005 Jul;85(3):845-81
15987797
J Biol Chem. 2005 Feb 18;280(7):5406-13
15583007
PPAR Res. 2008;2008:295784
18382616
Exp Biol Med (Maywood). 2004 Nov;229(10):1053-60
15522842
J Inflamm (Lond). 2005 Nov 25;2:15
16309552
J Clin Invest. 2006 Feb;116(2):369-77
16424942
J Lipid Res. 2004 Dec;45(12):2161-73
15489539
Prog Retin Eye Res. 2010 May;29(3):191-207
20096366
PPAR Res. 2008;2008:720163
18382621