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Abbot F Clark; The role of cadherins in glaucomatous trabecular signaling and the regulation of IOP. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1365.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
We previously reported that inhibition of canonical Wnt signaling in the TM (via increased expression of Wnt antagonists SFRP1 and DKK1) elevates IOP. However, the molecular mechanisms responsible for this ocular hypertension are undefined. β-catenin serves as the major mediator of canonical Wnt signaling, but β-catenin also plays an essential role in tethering cell-cell cadherin complexes to the actin cytoskeleton. Therefore, there is a convergence of Wnt, β-catenin, and cadherin pathways. Cadherin complexes are mechanotransducers regulating tissue compliance. We have begun to test the innovative hypothesis that inhibition of Wnt signaling perturbs β-catenin and cadherin complexes in the TM and that this is the molecular mechanism responsible for elevated IOP. We have also determined the role of individual cadherins that are expressed in the TM in the regulation of IOP. Better understanding of this novel molecular pathway involved in glaucoma pathogenesis will lead to the discovery of unique disease modifying therapeutic strategies that could intervene and perhaps reverse glaucomatous damage to the trabecular meshwork
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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