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P. Wong, P. Lagali, J. Dunlevy, M. Chrenek; FAM46 Related Genes Are Induced by Oxidative Stress in ARPE-19 Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5075.
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© ARVO (1962-2015); The Authors (2016-present)
C6orf37 is a novel gene we identified in our search for the STGD3 disease gene a few years ago. Recently the gene was renamed to FAM46A. FAM46A is the first member of a novel gene family that includes FAM46B, FAM46C, and FAM46D. In the current study we characterize the FAM46A gene family with respect to retina and RPE expression.
A full molecular analysis of FAM46A was performed using standard molecular and bioinfomatic methodologies. To define the spatial expression of the FAM46 family of genes in the retina, we used quantitative RT-PCR (qRT-PCR) to measure the abundance of each transcript in RNA isolated from human retina and RPE. For characterization of RPE cell expression of FAM46 gene members in response to oxidative stress, we treated ARPE-19 cells with 500 uM tert-butylhydroperoxide (tBH) over a 10 hour time course that induces oxidative stress. RNA was extracted from the cells and qRT-PCR used to measure transcript abundance.
FAM46A is an evolutionarily conserved gene organized into 3 exons. Northern analysis revealed that FAM46A is widely expressed in the body and in the eye is more highly expressed in the retina than in the RPE. qRT-PCR analysis verified the FAM46A profile and revealed that FAM46B is more highly expressed in the retina than the RPE, FAM46C is more highly expressed in the RPE than the retina, and that FAM46D is not detectable in either tissue. FAM46A, FAM46B, and FAM46C expression were all elevated in ARPE-19 cells treated with tBH. Analyses of a tBH treatment profile of ARPE-19 cells revealed that there are slight differences in the profile of induced gene expression for all three of these genes.
With respect to retina and RPE, FAM46A and FAM46B are retinal enriched genes and FAM46C is a RPE enriched expressed gene. In ARPE-19 cells, all three genes are responsive to oxidative stress. Given the association of oxidative stress and aging, the FAM46 gene family may have a functional role in the aging eye and potentially age related macular degeneration.
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