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bioRxiv · 10.1101/2020.04.17.046383

Obstructed tear duct causes epiphora and precocious eyelid opening due to disruption of Prickle 1-mediated Wnt/PCP signaling

Guo, D.·Ru, J.·Fan, J.·Ju, R.·Jin, K.·Ouyang, H.·Wei, L.·Liu, Y.·Liu, C.
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Abstract

The tear drainage apparatus evolved in terrestrial animals serving as conduits for tear flow. Obstruction of tear drainage causes a range of ocular surface disorders. Hitherto, genetics of tear duct development and obstruction has been scarcely explored. Here we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to blockage of the tear drainage by the incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (CL). Further analysis revealed that the precocious eyelid opening, previously observed in the same type of Prickle 1 mutants, is also caused by tear duct dysplasia. A comparison of wild type, the Prickle 1 hypomorph and null mutants revealed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. As a key component of a set of six Wnt/PCP core proteins, Prickle 1 usually works together with other PCP components. An investigation of expression of Wnt/PCP core genes demonstrated three of the six PCP components in tear duct, supporting the notion of context-dependent organization of PCP protein complexes. Furthermore, expression of Fgfr2/Fgf10 and p63 genes, mutations of which are associated with NLD and CL hypoplasia in human, were not altered in Prickle 1 mutant mice. Lastly, we showed that Prickle 1 expression in developing tear drainage system is conserved between mouse and human despite anatomical differences. Altogether, the study uncovered how obstruction of the tear drainage could lead to a complex ocular surface disorder, which may have genetic implications in human ocular health.

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Guo, D., Ru, J., Fan, J., Ju, R., Jin, K., Ouyang, H., Wei, L., Liu, Y., Liu, C.. 2020-04-17. Obstructed tear duct causes epiphora and precocious eyelid opening due to disruption of Prickle 1-mediated Wnt/PCP signaling. https://doi.org/10.1101/2020.04.17.046383

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