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Maria Muccioli, Timothy F. Plageman; Requirements for cellular folate during lens development. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3062.
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© ARVO (1962-2015); The Authors (2016-present)
Dietary folate deficiency is linked to morphogenetic birth defects, however the cellular role folate plays during development is unknown. Cataract formation has also been linked reduced dietary folate. To determine what role folate intake has on lens development, conditional ablation of the folate receptor gene, Folr1 was performed in the embryonic lens.
Immunofluorescent staining was performed on histological sections of embryonic and adult Le-cre; Folr1flox/flox and on transfected epithelial cells.
While lens development appears to progress normally until embryonic development day 15, E16.5 stage embryos exhibit smaller lenses and aberrant cellular organization of the lens fibers. Furthermore, adult mutant eyes are microphthalmic, have pronounced eye recession, and cataracts. In vitro experiments have indicated that Folr1 increases the phosphorylation of non-muscle myosin in a Rock-independent manner specifically through the activation of myosin light chain kinase. Ongoing efforts are focused at determining whether myosin activation is disrupted by the absence of Folr1 in embryonic lenses.
Folate is a necessary metabolite for the development of the lens and requires intake through the Folr1 receptor. Because the absence of Folr1 causes severe lens fiber disorganization, it is possible that the lens maintains cellular organization through folate-dependent stimulation of actomyosin filaments.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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