July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Altered expression of aquaporins in glaucomatous trabecular meshwork correlates to fibrotic genes and is regulated by Wnt signalling
Author Affiliations & Notes
  • Shaika Shanbagh
    GROW LAB, NARAYANA NETHRALAYA FOUNDATION, BANGALORE, KARANATAKA, India
  • RAJESH SASI KUMAR
    GLAUCOMA, NARAYANA NETHRALAYA, BANGALORE, KARANATAKA, India
  • Sushma Tejwani
    GLAUCOMA, Narayana Nethralaya Eye Hospital, BANGALORE, karnataka, India
  • Praveen Machiraju
    GROW LAB, NARAYANA NETHRALAYA FOUNDATION, BANGALORE, KARANATAKA, India
  • Rohit Shetty
    CORNEA, NARAYANA NETHRALAYA , BANGALORE, KARANATAKA, India
  • Arkasubhra Ghosh
    GROW LAB, NARAYANA NETHRALAYA FOUNDATION, BANGALORE, KARANATAKA, India
  • Footnotes
    Commercial Relationships   Shaika Shanbagh, None; RAJESH SASI KUMAR, None; Sushma Tejwani, None; Praveen Machiraju, None; Rohit Shetty, None; Arkasubhra Ghosh, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3534. doi:
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      Shaika Shanbagh, RAJESH SASI KUMAR, Sushma Tejwani, Praveen Machiraju, Rohit Shetty, Arkasubhra Ghosh; Altered expression of aquaporins in glaucomatous trabecular meshwork correlates to fibrotic genes and is regulated by Wnt signalling. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3534.

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

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Abstract

Purpose : Elevated intraocular pressure in glaucoma patients is caused by impaired aqueous humor outflow through trabecular meshwork (TM) cells resulting in optic nerve damage and visual field loss. Water and solute transport is controlled by the Aquaporin (AQP) protein family. Therefore, we investigated the levels of AQP 6, 9 and 0 in glaucoma and their molecular regulation in TM cells.

Methods : All human tissue samples were collected after approval of the Institutional Ethics Committee and informed consent. Trabecular meshwork samples were obtained from 47 patients undergoing glaucoma filtration surgery. 26 non disease donor eyes served as controls. Gene expression analysis was done for aquaporins (AQP0, 6, 9) and compared to known disease related pro-fibrotic genes (LOX, SPARCL2, LOXL2, CTGF), Wnt target AXIN2, and IL-6. Primary human TM cells in culture were treated with Wntmodulators (AZD2858 and XAV939), TNFα(10ng/ml) and TGFβ(10ng/ml) followed by QPCR and immunoblotting for pathway activation and AQP expression. Fibrotic function of TM cells after treatment was analysed by collagen gel contraction assays.

Results : Glaucoma TM samples had increased AQP6 (p≤0.03) and AQP9 (p≤0.04) expression, but AQP0was not altered. IL-6(p≤0.045) and AXIN2(p=0.044) levels were higher in patient along with LOX, LOXL2indicating co-regulation of Wnt, pro-fibrotic and inflammatory pathways.We observed significant positive correlation between the AQP6 and AQP9 (P≤0.0001),IL-6 and AQP-9 (p≤0.0001),LOX and CTGF(P≤0.006),LOXL2 and CTGF (p≤0.0007) as well asLOXL2 and LOX(p≤0.001). TGFβ treatment in cultured TM cells increased fold change in expression of AQP-6 (1.31), AQP9 (1.41),AQP0 (1.82)and AXIN2(1.45). TNFαtreatment also increased AQP0(1.36) and AQP9(1.5). Wnt modulation by AZD2858 and XAV939altered expression of all aquaporins, with positive AXIN2 expression. XAV939 induced AQP6 and AQP9 expression while AZD939 repressed expression. The various treatments differentially affected the extent of collagen gel contraction.

Conclusions : AQP6, and AQP9 expression is altered in glaucomatous TM tissue, which correlates with profibrotic gene levels and Wnt activity suggesting a novel transcriptional regulatory network in disease. The data support the possibility of targeting the Wnt pathway for glaucoma therapy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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