Low availability of choline in utero disrupts development and function of the retina.

Szczegóły
Abstrakt

Tytuł:: Low availability of choline in utero disrupts development and function of the retina.
Autorzy:: Trujillo-Gonzalez I; Nutrition Research Institute, University of North Carolina-Chapel Hill, Kannapolis, North Carolina, USA.
Friday WB; Nutrition Research Institute, University of North Carolina-Chapel Hill, Kannapolis, North Carolina, USA.
Munson CA; Nutrition Research Institute, University of North Carolina-Chapel Hill, Kannapolis, North Carolina, USA.
Bachleda A; Department of Cell Biology and Physiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Weiss ER; Department of Cell Biology and Physiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Alam NM; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA.; Center for Visual Restoration, Burke Neurological Institute, White Plains, New York, USA.
Sha W; Bioinformatics Services Division, University of North Carolina-Charlotte, Kannapolis, North Carolina, USA.
Zeisel SH; Nutrition Research Institute, University of North Carolina-Chapel Hill, Kannapolis, North Carolina, USA.; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Surzenko N; Nutrition Research Institute, University of North Carolina-Chapel Hill, Kannapolis, North Carolina, USA.; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Źródło:: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2019 Aug; Vol. 33 (8), pp. 9194-9209. Date of Electronic Publication: 2019 May 15.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural
Język:: English
Imprint Name(s):: Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley
Original Publication: [Bethesda, Md.] : The Federation, [c1987-
MeSH Terms:: Choline Deficiency/*embryology
Retina/*abnormalities
Animals ; Cell Cycle/physiology ; Cell Differentiation/physiology ; Choline/administration & dosage ; Choline/metabolism ; Choline Deficiency/physiopathology ; Diet ; Down-Regulation ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurofibromin 2/genetics ; Neurofibromin 2/metabolism ; Neurogenesis/physiology ; Pregnancy ; Retina/embryology ; Retina/physiopathology ; Retinal Cone Photoreceptor Cells/ultrastructure ; Retinal Ganglion Cells/cytology ; Retinal Ganglion Cells/physiology ; Stem Cells/cytology ; Stem Cells/physiology
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Grant Information:: P30 CA016086 United States CA NCI NIH HHS; P30 DK056350 United States DK NIDDK NIH HHS; P30 ES010126 United States ES NIEHS NIH HHS; R01 DK115380 United States DK NIDDK NIH HHS
Contributed Indexing:: Keywords: Nf2/Merlin; maternal nutrition; retinal development; visual sensitivity
Substance Nomenclature:: 0 (Neurofibromin 2)
N91BDP6H0X (Choline)
Entry Date(s):: Date Created: 20190517 Date Completed: 20200601 Latest Revision: 20240214
Update Code:: 20240214
PubMed Central ID:: PMC6662989
DOI:: 10.1096/fj.201900444R
PMID:: 31091977
: Czasopismo naukowe

Adequate supply of choline, an essential nutrient, is necessary to support proper brain development. Whether prenatal choline availability plays a role in development of the visual system is currently unknown. In this study, we addressed the role of in utero choline supply for the development and later function of the retina in a mouse model. We lowered choline availability in the maternal diet during pregnancy and assessed proliferative and differentiation properties of retinal progenitor cells (RPCs) in the developing prenatal retina, as well as visual function in adult offspring. We report that low choline availability during retinogenesis leads to persistent retinal cytoarchitectural defects, ranging from focal lesions with displacement of retinal neurons into subretinal space to severe hypocellularity and ultrastructural defects in photoreceptor organization. We further show that low choline availability impairs timely differentiation of retinal neuronal cells, such that the densities of early-born retinal ganglion cells, amacrine and horizontal cells, as well as cone photoreceptor precursors, are reduced in low choline embryonic d 17.5 retinas. Maintenance of higher proportions of RPCs that fail to exit the cell cycle underlies aberrant neuronal differentiation in low choline embryos. Increased RPC cell cycle length, and associated reduction in neurofibromin 2/Merlin protein, an upstream regulator of the Hippo signaling pathway, at least in part, explain aberrant neurogenesis in low choline retinas. Furthermore, we find that animals exposed to low choline diet in utero exhibit a significant degree of intraindividual variation in vision, characterized by marked functional discrepancy between the 2 eyes in individual animals. Together, our findings demonstrate, for the first time, that choline availability plays an essential role in the regulation of temporal progression of retinogenesis and provide evidence for the importance of adequate supply of choline for proper development of the visual system.-Trujillo-Gonzalez, I., Friday, W. B., Munson, C. A., Bachleda, A., Weiss, E. R., Alam, N. M., Sha, W., Zeisel, S. H., Surzenko, N. Low availability of choline in utero disrupts development and function of the retina.

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