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Alon Kahana, Daniel S. Kasprick, Phillip E. Kish, Donika D. Gallina; Tissue Remodeling And Gene Expression Profiling Of A Regenerating Extraocular Muscle In Zebrafish. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1561.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize tissue remodeling characteristics and gene expression profile of regenerating zebrafish extraocular muscles (EOMs).
Adult zebrafish expressing green fluorescent protein (GFP) in EOMs underwent lateral rectus myectomy followed by sequential microscopic characterization using differential interference microscopy. Laser microdissection and surgical techniques were used to obtain tissue from pre- and post-regenerative lateral recti, which was used for microarray gene expression analysis. Validation was achieved by in situ hybridization, RT-PCR, and embryo knockdown experiments.
Surgically-damaged lateral rectus muscle recovered its morphology in 5-7 days, coinciding with functional recovery of pursuit and saccade movements. Following myectomy, the remaining muscle underwent extensive remodeling, including loss of cell shape and decrease in cell size. Extensive proliferation ensued at the leading edge of the regenerating muscle. Gene expression profiling revealed that myogenic genes were downregulated, while genes involved in formation of the extracellular matrix were upregulated. Transcription factors involved in epithelial-mesenchymal transition, proliferation, and metabolism were upregulated. Some, but not all, upregulated transcription factors were found to be necessary for embryonic EOM development, revealing both similarities and differences between embryonic development and adult regeneration processes.
Zebrafish EOM regeneration occurs rapidly and with complete functional recovery. This is an excellent in vivo model for identifying the key processes that control EOM repair and regeneration following severe injury. Improved understanding of EOM repair and regeneration may lead to development of novel therapies for acquired strabismus (causing diplopia) and congenital strabismus (causing amblyopia).
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