title: Neonatal aphakia retards ocular growth and alters scleral gene expression in rhesus monkeys.
abstract: OBJECTIVE
  We hypothesize that remodeling of the scleral extracellular matrix, involving collagen and proteoglycan synthesis and turnover, is a key process involved in ocular growth. Decreased axial elongation is observed following neonatal removal of the crystalline lens in a rhesus monkey model of congenital cataract. We wanted to determine changes in gene expression in the operated and companion eye following lensectomy, especially for extracellular matrix in the sclera.
  
  
  METHODS
  Between 4 and 7 days of age, infant monkeys underwent surgical removal of the lens from the right eye. Axial lengths of the operated and unmanipulated fellow eyes were measured and when interocular differences of >0.4 mm were achieved, monkeys were sacrificed and RNA was isolated from sclera. In order to determine changes in scleral gene expression in aphakic versus control eyes, we used Clontech's Atlas Gene Array (Human Cancer Array version 1.2) hybridized with total RNA from three monkeys.
  
  
  RESULTS
  Atlas Gene Array analysis demonstrated differential expression of several genes in the operated versus the unmanipulated eye. Most notably, there was a statistically significant increase in expression of several extracellular matrix (ECM) genes including: aggrecan, decorin, biglycan, several collagens, and tenascin in the RNA from the sclera of the aphakic eyes when compared to the unmanipulated eyes. Genes for several matrix metalloproteinases (MMPs) showed no significant change following lens removal although there was a trend towards decreased expression. There were also statistically significant changes in the pattern of gene expression in the operated eye relative to the unmanipulated eye for cell adhesion, cell cycle, apoptosis, and cytoskeleton transcripts.
  
  
  CONCLUSIONS
  Our results suggest that removal of the crystalline lens alters gene expression in the sclera with a prominent upregulation of ECM transcripts. These data support recent evidence that remodeling of the ECM composition of the sclera may be an important regulator of ocular growth.
authors.affiliation: Health Research Institute, Orlando Regional Healthcare, Orlando, FL 32806, USA. rtarnuzz@orhs.org
authors.forename: Roy W
authors.initials: RW
authors.lastname: Tarnuzzer
authors.forename: Alcides
authors.initials: A
authors.lastname: Fernandes
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.forename: Scott R
authors.initials: SR
authors.lastname: Lambert
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001035:Aphakia / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000254:growth & development*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007908:Lens, Crystalline / Q000601:surgery; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D012590:Sclera / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D012333:RNA, Messenger; D012313:RNA