title: Estrogens reduce the expression of YKL-40 in the retina: implications for eye and joint diseases.
abstract: OBJECTIVE
  To identify modifications in the gene expression profile of the ocular posterior segment in ovariectomized (OVX) mice with and without substitutive estradiol therapy and to select differentially expressed genes that could be relevant to the natural history of human age-related macular degeneration (AMD).
  
  
  METHODS
  Chorioretinal tissues from two groups of 25 treated and untreated OVX mice were analyzed by using cDNA array technology. The expression level of selected genes was confirmed in triplicate by RT-PCR and related to the estrogenic status of the animals. Expression of the YKL-40 gene was further investigated in intact or diseased human retinas and in a murine model of experimental choroidal neovascularization (CNV), using laser pressure catapulting.
  
  
  RESULTS
  Of the approximately 10,000 genes screened, only YKL-40 expression was significantly downregulated by 17-beta-estradiol. YKL-40 was expressed in intact human neural retina and in the RPE. The expression of YKL-40 was upregulated in experimental CNV and in neovascular membranes extracted from patients affected by the exudative form of AMD.
  
  
  CONCLUSIONS
  These observations indicate that YKL-40 expression in the retina is modulated by serum levels of estradiol. This protein could be relevant to the development of AMD and is also a new mediator to take into account when evaluating the broad consequences of hormonal replacement therapy.
authors.affiliation: Department of Ophthalmology, University Hospital, Sart-Tilman, Liège, Belgium. jmrakic@chu.ulg.ac.be
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Rakic
authors.forename: Vincent
authors.initials: V
authors.lastname: Lambert
authors.forename: Manuel
authors.initials: M
authors.lastname: Deprez
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
mesh_terms: D054392:Adipokines; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000071451:Chitinase-3-Like Protein 1; D020256:Choroidal Neovascularization / Q000378:metabolism*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D037102:Lectins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D012333:RNA, Messenger; D004958:Estradiol