title: Image defocus and altered retinal gene expression in chick: clues to the pathogenesis of ametropia.
abstract: OBJECTIVE
  Because of the retina's role in refractive development, this study was conducted to analyze the retinal transcriptome in chicks wearing a spectacle lens, a well-established means of inducing refractive errors, to identify gene expression alterations and to develop novel mechanistic hypotheses about refractive development.
  
  
  METHODS
  One-week-old white Leghorn chicks wore a unilateral spectacle lens of +15 or -15 D for 6 hours or 3 days. With total RNA from the retina/(retinal pigment epithelium, RPE), chicken gene microarrays were used to compare gene expression levels between lens-wearing and contralateral control eyes (n = 6 chicks for each condition). Normalized microarray signal intensities were evaluated by analysis of variance, using a false discovery rate of <10% as the statistical criterion. Selected differentially expressed genes were validated by qPCR.
  
  
  RESULTS
  Very few retina/RPE transcripts were differentially expressed after plus lens wear. In contrast, approximately 1300 transcripts were differentially expressed under each of the minus lens conditions, with minimal overlap. For each condition, low fold-changes typified the altered transcriptome. Differentially regulated genes under the minus lens conditions included many potentially informative signaling molecules and genes whose protein products have roles in intrinsic retinal circadian rhythms.
  
  
  CONCLUSIONS
  Plus or minus lens wear induce markedly different, not opposite, alterations in retina/RPE gene expression. The initial retinal responses to defocus are quite different from those when the eye growth patterns are well established, suggesting that different mechanisms govern the initiation and persistence or progression of refractive errors. The gene lists identify promising signaling candidates and regulatory pathways for future study, including a potential role for circadian rhythms in refractive development.
authors.affiliation: Department of Ophthalmology, University of Pennsylvania School of Medicine, Scheie Eye Institute, Philadelphia, Pennsylvania 19104-6075, USA. stone@mail.med.upenn.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stone
authors.forename: Alice M
authors.initials: AM
authors.lastname: McGlinn
authors.forename: Donald A
authors.initials: DA
authors.lastname: Baldwin
authors.forename: John W
authors.initials: JW
authors.lastname: Tobias
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.forename: Tejvir S
authors.initials: TS
authors.lastname: Khurana
mesh_terms: D000818:Animals; D002645:Chickens; D002940:Circadian Rhythm / Q000235:genetics; D004195:Disease Models, Animal; D005139:Eyeglasses; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards; D012029:Refraction, Ocular / Q000235:genetics*; D012030:Refractive Errors / Q000209:etiology / Q000235:genetics*; D012160:Retina / Q000254:growth & development / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000592:standards; D015398:Signal Transduction / Q000235:genetics