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Daniel Chauss, Subhasree Basu, Lisa Brennan, A Menko, Marc Kantorow; The temporal and spatial range and spectrum of autophagy and mitophagy genes expressed during lens cell differentiation and development. Invest. Ophthalmol. Vis. Sci. 2013;54(15):478.
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© ARVO (1962-2015); The Authors (2016-present)
Considerable evidence now suggests that autophagy is important for those developmental and transparent functions of the ocular lens that require organelle degradation and recycling of cellular components. This study was conducted to identify those functional genetic networks that govern autophagy-mediated organelle degradation and development of the eye lens.
Functional gene clustering was performed on data obtained from DNA microarray analysis (Affymetrix U133a chips) of total RNA extracted from adult human lens epithelia and fiber cells. Functional gene clustering was also performed on data obtained from RNA sequencing (whole transcriptome sequencing analysis) performed on days 8, 9, 10, 11,12 and 15 day chick embryos and on day 13 chick embryos lenses microdissected into central lens epithelium, equatorial epithelium, cortical fibers and central fibers. The temporal and spatial levels of specific transcripts were further evaluated by quantitative RT-PCR, western analysis, immunohistochemistry of whole lenses and dual-color confocal microscopy of whole lenses.
The lens expresses functional clusters of transcripts that collectively encode those proteins required for autophagy induction, formation of autophagosomes, transport of autophagosomes and mitophagy. Functional gene clusters involved in multiple autophagy pathways are expressed throughout the lens. These include those participating in the classic ATG5-dependent, the alternative ATG-5-independent and the chaperone-mediated autophagy pathways. These functional gene clusters exhibit asymmetric expression patterns in different stages of lens development and between undifferentiated lens epithelia and differentiating lens fiber cells.
These data provide evidence that specific functional autophagy gene clusters orchestrate the recycling of lens organelles and other cellular components required for lens development, differentiation and maintenance. Since these processes are critical for the transparent function of the lens, loss of function of the identified genes is likely a key factor in cataract formation.
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