June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Rescue of Lysyl Oxidase levels by Batimastat and Trehalose treatment in human corneal stromal tissue and cell models: implications for Keratoconus therapy
Author Affiliations & Notes
  • NITHIN KIRAN
    Grow research Lab, Narayana Nethralaya Foundation, Bangalore, karanataka, India
  • Rohit Shetty
    Cornea and Refractive surgery, Narayana Nethralaya, Bangalore, Karnataka, India
  • Pooja Khamar
    Cornea and Refractive surgery, Narayana Nethralaya, Bangalore, Karnataka, India
  • Arkasubhra Ghosh
    Grow research Lab, Narayana Nethralaya Foundation, Bangalore, karanataka, India
  • Footnotes
    Commercial Relationships   NITHIN KIRAN None; Rohit Shetty None; Pooja Khamar None; Arkasubhra Ghosh None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4255. doi:
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      NITHIN KIRAN, Rohit Shetty, Pooja Khamar, Arkasubhra Ghosh; Rescue of Lysyl Oxidase levels by Batimastat and Trehalose treatment in human corneal stromal tissue and cell models: implications for Keratoconus therapy. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4255.

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

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Abstract

Purpose : Purpose: Keratoconus(KC) is a progressive, corneal, ectatic disorder characterized by increased MMP9 and reduced Lysyl oxidase(LOX) in patients. To rescue LOX expression and inhibit inflammatory signaling, we tested an MMP inhibitor Batimastat(BST) and the inflammation regulator Trehalose(TRE).

Methods : Methodology: Corneal stromal lenticules from donors undergoing SMILE refractive surgeries were treated with TRE and BST for 3 weeks and assessed for expression of LOX, MMP9 and Collagens under chronic inflammatory stress. Primary fibroblasts(HCF) derived from control and KC corneas were analyzed for gene/protein expression and collagen gel contractility when treated with BST/TRE. Human corneal epithelial cells(HCE-T) under chronic inflammation with and without BST/TRE treatment were assessed for LOX, Collagens, MMP9 and phosphorylated MAPK(p38), NFκB(p65) and AKT by immunoblotting.

Results : Results: Inflammatory stimuli significantly enhanced MMP9 and reduced LOX levels in ex-vivo donor stromal lenticules and well as corneal cell types. TRE and BST treatment significantly reduced MMP9 levels which consequently increased LOX and Collagen expression in lenticules under basal and inflammatory stress. Donor control HCF and KC-HCF treated with BST significantly increased LOX levels as well as collagen gel contraction. TRE and BST treatment reduced phosphorylation of p65 and p38 under chronic inflammatory stress in HCE-T cells leading to significantly enhanced LOX and Collagen expression.

Conclusions : Conclusion: Chronic inflammatory signalling including excess MMP9 production transcriptionally suppresses LOX production in corneal stroma. Since TRE and BST rescued LOX and Collagen expression while inhibiting MMP9 via p38 and p65 pathways, they may be a novel therapeutic modality for KC.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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