Investigative Ophthalmology & Visual Science Cover Image for Volume 60, Issue 9
July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Keratoconus: New insights in the underlying pathomechanism
Author Affiliations & Notes
  • Uwe Hansen
    Institute for Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany
  • Melanie Timmen
    Institute for Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany
  • Martin Goette
    Department of Gynecology and Obstetrics, Germany
  • Richard Stange
    Institute for Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany
  • Thomas Pap
    Institute for Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany
  • Nicole Eter
    Department of Ophthalmology, Germany
  • Maged Alnawaiseh
    Department of Ophthalmology, Germany
  • Footnotes
    Commercial Relationships   Uwe Hansen, None; Melanie Timmen, None; Martin Goette, None; Richard Stange, None; Thomas Pap, None; Nicole Eter, None; Maged Alnawaiseh, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 353. doi:
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    • Get Citation

      Uwe Hansen, Melanie Timmen, Martin Goette, Richard Stange, Thomas Pap, Nicole Eter, Maged Alnawaiseh; Keratoconus: New insights in the underlying pathomechanism. Invest. Ophthalmol. Vis. Sci. 2019;60(9):353.

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

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Abstract

Purpose : In keratoconus (KC), structural and compositional changes leads to disruptions of the lamellar organization with thinning and scarring of the central part of the cornea. The underlying pathomechnism is unknown. Both genetic and environmental factors have been associated with KC and recent studies suggest that also inflammatory conditions, e.g. high TNF-α level, might play a role in the onset of KC. In order to get more insights and to find mouse model for KC, we analysed the corneas of hTNFtg mice as well as of syndecan-1 and -4 deficient mice.

Methods : The suprastructural organization of the corneas of hTNFtg, syndecan-1 and -4 deficient mice as well as of KC patients were analysed by transmission electron microscopy (TEM). The degradation of collagens in the stroma was visualized by the collagen hybridizing peptide B-CHP. Moreover, 3D-cell cultures of isolated human keratocytes were analysed by TEM and for activity of the cross-linking tissue transglutaminase (TG).

Results : Sheets of orthogonally arranged collagen fibrils were found in the stroma of wild-type mice and human controls. In contrast, lamellae were disrupted and mean fibril diameter increased in hTNFtg as well as in both syndecan-deficient mice. Interestingly, the stroma morphology of hTNFtg mice was very similar to that found in KC patients. Moreover, we found an invasion of macrophages and keratocytes showed signs of apoptosis. 3D-cell cultures of KC keratocytes generated a structurally altered ECM with reduced TG-activity in contrast to controls. In addition, binding of B-CHP was stronger in KC as well as in hTNFtg mice. Moreover, alterations in the epithelium with disrupted cell-cell-contacts and alterations in the Bowman`s membrane were found in all analysed mouse models.

Conclusions : The disruption of the lamellar organization of collagen fibrils in hTNFtg, syndecan-1 and -4 deficient mice is similar to that found in the stroma of KC patients. Thus, inflammatory factors and altered cross-links could be crucial for the onset of KC. The stronger higher binding B-CHP supports our hypothesis of an enhanced degradation of collagens in the stroma. Therefore, further analysis of hTNFtg mice as a mouse model for KC will help to understand the underlying pathomechanisms of KC. Moreover, analysis of syndecan-deficient mice will provide new insights in the mechanisms of lamellae formation and fibril diameter control.

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

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