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BACKGROUND: The ANGPT (angiopoietin)-TEK (tyrosine kinase, endothelial) vascular signaling pathway plays a key role in the formation of Schlemm canal, and loss-of-function mutations in the or gene are associated with primary congenital glaucoma in children. In genome-wide association studies, an association was identified between protection from primary open-angle glaucoma and the single-nucleotide polymorphism rs76020419 (G>T), located within a predicted -binding site in the 3' untranslated region of . To date, the functional impact of this variant in the anterior chamber of the eye remains largely unexplored.METHODS: MT (mutant) mice harboring an orthologous rs76020419 minor allele (T) were generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9). Plasma and tissue samples, including eyes, were collected, and ANGPT2 expression was quantified using ELISA. Anterior segments from eyes were collected from WT (wild-type) and MT mice, and Schlemm canal area was quantified.RESULTS: In the MT group, higher ANGPT2 concentrations were observed in the plasma, lungs, kidneys, and eyes (=0.0212, <0.001, =0.0815, and =0.0215, respectively). Additionally, the Schlemm canal was larger in MT mice compared with WT mice (=0.0430).CONCLUSIONS: The rs76020419 minor allele (T) is associated with increased levels of ANGPT2 and a larger Schlemm canal in mice. These findings suggest a potential protective mechanism in glaucoma.