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MD Fischer, JR Gorospe, E Felder, S Bogdanovich, F Pedrosa-Domellöf, RS Ahima, NA Rubinstein, EP Hoffman, TS Khurana; Expression Profiling Reveals Metabolic and Structural Components of Extraocular Muscles . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1910.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The extraocular muscles (EOM) are small, specialized muscles that are anatomically and physiologically distinct from other mammalian skeletal muscles. EOM are preferentially affected in the mitochondrial myopathies, but are enigmatically spared in Duchenne's muscular dystrophy. EOM group specific properties have been attributed to a unique molecular makeup; an allotype. The purpose of this study was to define the expression profile of EOM and analyze their group specific properties at the mRNA level. Methods:We used Affymetrix GeneChips to analyze the expression profile of ∼ 26,500 genes and ESTs in rat EOM. Structural and biochemical methods were used to validate the results on protein/substrate level. Results:We found 190 genes and 146 ESTs to be differentially expressed in rat EOM when compared to limb muscle, based on a 2-fold difference cutoff and sequential iterative comparisons to eliminate false positives. Detection of upregulation of genes such as EOM-specific and Embryonic MyHC suggests that the profile was extremely comprehensive compared to previous attempts at expression profiling. Conclusion:The expression profile was highly concordant with known structural characteristics of EOM. Catalytic enzymes and structural elements required for efficient, fatigue resistant, oxidative metabolism were upregulated in EOM, while genes for glycogen metabolism were decreased. The use of such a metabolic pattern in EOM was verified using biochemical and structural methods. EOM also showed increased expression of genes related to muscle regeneration such as FGFR1, IGF1 and IGF binding proteins as well as the satellite cell marker VCAM1. The characterization of the EOM expression profile helps to define gene transcription patterns associated with the unique anatomical, metabolic and patho-physiological properties of EOM and supports the existence of an EOM-specific allotype.
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