July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The role of Wnt signaling in TGFβ2-induced ocular hypertension
Author Affiliations & Notes
  • Weiming Mao
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
    Eugene & Marilyn Glick Eye Institute, Indiana, United States
  • Naga Pradeep Rayana
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
    Eugene & Marilyn Glick Eye Institute, Indiana, United States
  • Jinzi Wu
    University of North Texas Health Science Center, Texas, United States
  • Amanda Roberts
    University of North Texas Health Science Center, Texas, United States
  • Rafal Fudala
    University of North Texas Health Science Center, Texas, United States
  • Footnotes
    Commercial Relationships   Weiming Mao, None; Naga Pradeep Rayana, None; Jinzi Wu, None; Amanda Roberts, None; Rafal Fudala, None
  • Footnotes
    Support  NIH/NEI grant 5R01EY026962-02 (W.M.)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5133. doi:https://doi.org/
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      Weiming Mao, Naga Pradeep Rayana, Jinzi Wu, Amanda Roberts, Rafal Fudala; The role of Wnt signaling in TGFβ2-induced ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5133. doi: https://doi.org/.

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

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Abstract

Purpose : In primary open angle glaucoma (POAG), the most important risk factor is elevated intraocular pressure (IOP). TGFβ2 and sFRP1, the ligand for the TGFβ signaling pathway and inhibitor for the Wnt signaling pathway, respectively, are elevated in POAG trabecular meshwork (TM). We previously showed that TGFβ and Wnt signaling pathways cross-inhibit each other in the TM. Here, we determined whether Wnt signaling is able to inhibit TGFβ2-induced ocular hypertension (OHT) and its potential mechanism.

Methods : Ad5-CMV-NULL/mWnt3a/mutant hTGFβ2 viruses were injected individually or as a mixture into the vitreous chamber of C57BL/6 mice. Mice IOP was measured under anesthesia using a TonoLab tonometer. Also, paired non-POAG human donor eyes were perfused with DMEM containing 100ng/ml Wnt3a and/or 5ng/ml TGFβ2. IOP was recorded using pressure transducers. Fluorescent protein tagged Smad4 and β-catenin were co-expressed in TM cells for Forster resonance energy transfer (FRET) study.

Results : In female mouse eyes, viral transduction with Ad5-TGFβ2 induced OHT while Ad5-Wnt3a co-transduction decreased TGFβ2-induced OHT (n=5, p<0.05). In perfusion cultured human eyes, recombinant TGFβ2 also induced OHT in one eye while Wnt3a co-treatment either prevented or delayed OHT in the fellow eye (n=2). FRET studies indicated that Smad4 and β-catenin, the key mediators for the TGFβand Wnt pathways, may form a protein complex in TM cells.

Conclusions : Wnt signaling seems to antagonize TGFβ signaling in IOP regulation. More studies are required to further determine how the two pathways balance each other’s activities and maintain proper IOP.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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