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S. Khanna, G. Cheng, M. Mustari, J. Porter; Expression Profiling in Extraocular Muscle of Control and Amblyopic Monkeys . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4810.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: : Extraocular muscle (EOM) maturation is, at least in part, shaped by activity patterns in developing visuomotor systems and is altered in a critical period-dependent fashion by manipulations that adversely affect visual cortex development. Here, we further tested EOM regulatory mechanisms by evaluating gene expression profiles in amblyopic monkey EOMs. Methods: Amblyopia was induced by rearing rhesus monkeys from birth with monocular eyelid suture (n = 2). Control animals (n = 2) were reared with normal visual experience. EOMs were harvested at 4 months for expression analysis using Affymetrix HG-U133A and B human microarrays, which contain oligonucleotide probes with sufficient sequence homology for use in the monkey. Rectus muscle layers were individually captured with laser microdissection and similarly evaluated. Results: Control medial (MR) and lateral (LR) rectus muscle expression signatures were nearly identical. MR and LR muscles from amblyopes showed only mild alterations from control among the 39,000 transcripts represented on the Affymetrix arrays. Numbers of repressed transcripts (LR: 36; MR: 25) exceed those that were induced (LR: 5; MR: 17) in both horizontal recti. Muscle-specific transcripts were differentially involved in the two rectus muscles. Calponin 3 (cytoskeleton) and jagged 1 (myogenesis) met stringent criteria for downregulation in MR only, while sarcolipin and EOM-specific myosin met selection criteria for LR only. Both muscles exhibited alterations in extracellular matrix-associated transcripts. Fibril-forming (Col1a1, Col1a2, Col3a1, Col5a2) and basement membrane (Col6a3) collagen transcripts were repressed in LR muscles of amblyopes, as were decorin, laminin 1, and fibronectin 1. Similar, albeit fewer, changes were noted in the extracellular matrix of MR muscles (Col1a2, Col15a1, fibronectin 1, metallothioneine 1X). Conclusions: Although EOM exhibits substantial critical period-dependent development in the rodent dark rearing model, only some of these changes were apparent in the less severe monocular eyelid suture model of amblyopia. While confirming the EOM-specific myosin dependence upon normal visuomotor development, our data establish that alterations in extracellular matrix proteins may be the most significant alteration in EOM of amblyopic monkeys.
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