June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Formation of glycine through serine-glycine biosynthesis is essential for transfer of single-carbon units to folate metabolism for early eye formation
Author Affiliations & Notes
  • Justine Chee
    Oakland University, Rochester, Michigan, United States
  • Louise Lanoue
    University of California Davis, Davis, California, United States
  • Dave Clary
    University of California Davis, Davis, California, United States
  • KC Kent Lloyd
    University of California Davis, Davis, California, United States
  • Ala Moshiri
    University of California Davis, Davis, California, United States
  • Footnotes
    Commercial Relationships   Justine Chee, None; Louise Lanoue, None; Dave Clary, None; KC Kent Lloyd, None; Ala Moshiri, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2284. doi:
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      Justine Chee, Louise Lanoue, Dave Clary, KC Kent Lloyd, Ala Moshiri; Formation of glycine through serine-glycine biosynthesis is essential for transfer of single-carbon units to folate metabolism for early eye formation. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2284.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The genes and pathways that contribute to early eye development are not well known. We hypothesize that screening of the International Mouse Phenotyping Consortium (IMPC) database for unique knockout mouse lines with embryonic eye defects will yield novel genes and pathways important for eye embryogenesis.

Methods : The IMPC web portal (impc.org) was interrogated for mouse embryos with ocular defects. Most of the eye abnormalities in knockout mouse embryos were small or absent eyes, findings most relevant to microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease in humans. A literature search was performed to determine which of these mouse knockouts have been reported previously and if there were eye abnormalities associated with them. In addition, a “gold standard” list was created based on clinical literature of established genes associated with congenital MAC spectrum disease in humans. Gene ontology, protein-protein interaction networks, and functional annotation bioinformatics microarray analysis were used to analyze the predicted relationship between 1. human orthologs of the IMPC mouse genes and 2. the gold-standard MAC spectrum human disease genes to identify biochemical pathways involved in eye embryogenesis.

Results : Screening of the IMPC database of over 7,000 knockout lines resulted in 63 unique genes associated with embryonic eye defects. The literature search showed that 41 of the 63 had previously published knockout mouse models, and 22 did not. Out of the 41 published knockout mouse models, only 13 of them noted ocular defects in the original publication, and 28 of them did not. Therefore, the 28 published knockouts which did not previously detect ocular abnormalities and the 22 unpublished knockouts together represent 50 novel genes that contribute to early eye development in mice. The literature search also resulted in 114 gold standard human MAC disease genes, which were vetted against the 63 IMPC genes to show that several of the IMPC genes reveal a critical role for serine-glycine biosynthesis in early eye formation.

Conclusions : The genetic underpinnings of MAC spectrum disease are incompletely understood, however, serine-glycine biosynthesis may be a novel pathway associated with early eye development. Analysis of this pathway may hasten the diagnosis and treatment of this congenital blinding disease.

This is a 2021 ARVO Annual Meeting abstract.

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