Abstract
Purpose :
Wnt/PCP is crucial for tissue morphogenesis. Yet its role in ocular adnexa is largely unknown. The purpose of the current studies is to address the role of Wnt/PCP in ocular structures and related pathogenesis
Methods :
Expression of Wnt/PCP genes was examined by in situ hybridization and immunohistochemistry. Tissue morphology was examined by H&E staining, electron microscopy and confocal microscopy. Ocular phenotypes of genetically engineered mouse with mutation in Prickle 1 gene were examined. Altered gene expression in the mutant tissues was revealed by RNAseq analysis. Statistical analysis was performed with Student’s t-test.
Results :
Multiple Wnt/PCP components were detected during ocular adnexa development. Delayed eyelid closure and precocious reopening were observed in Prickle 1 mutant mice. Ocular surface inflammation correlated with the timing of the mutant eyelid reopening. RNAseq analysis of the mutant cornea revealed an expression profile shared by a range of dermatological diseases. Severe tear duct dysgenesis was exhibited in the mutant mice.
Conclusions :
The phenotype of precocious eyelid reopening is independent from that of prenatal delayed eyelid closure in Prickle 1 mutant mice. Precocious eyelid reopening is caused by tear duct dysgenesis, which may involve multiple Wnt/PCP components. Ocular surface pathogenesis appears to be elicited by autologous necrotic eyelid debris due to premature eyelid reopening. Thus, Wnt/PCP signaling is not only directly involved in adnexa development, but also indirectly impacts ocular surface homeostasis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.