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Die Struktur der Extrazellulärmatrix bei Keratokonus

The extracellular matrix structure in keratoconus

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Zusammenfassung

Hintergrund

Keratokonus ist eine Hornhauterkrankung, die mit einer fortschreitenden Verdünnung der zentralen Kornea einhergeht. Es gibt Hinweise auf eine autosomal dominante Vererbung dieses Krankheitsbildes. Ziel unserer Arbeiten war es, den Bezug zwischen Genexpression und strukturellen Veränderungen der stromalen Extrazellulärmatrix herzustellen.

Methode

Aus der Hornhaut wurde stromale RNA (Keratokonus bzw. Kontrollmaterial) isoliert, in cDNA umgewandelt und mittels Laserscanning auf Biochips mit 5600 Genspezifitäten (Affymetrix) erfasst. Die strukturellen Untersuchungen erfolgten mit Hilfe der Laser-Scanning-Mikroskopie und der Transmissionselektronenmikroskopie.

Ergebnisse

In Keratokonushornhäuten waren verschiedene Komponenten der Extrazellulärmatrix (Kollagen XV, Metalloproteasen) herauf-, andere dagegen herunterreguliert (Kollagen IV (α1 und α3), Versican). Die morphologischen Veränderungen korrelierten mit den genetisch gewonnenen Daten. Die orthogonale Struktur der Kollagenfibrillen im anterioren und zentralen Teil der Hornhaut wies irreguläre Strukturen der Kollagenmatrix auf.

Schlussfolgerungen

Die Veränderungen in der Hornhaut sprechen für eine Deregulation der Matrixanordnung und lenken bei der Frage nach dem Ursprung dieser Krankheit das Interesse verstärkt auf die interfibrilläre Anordnung und damit auf das Zusammenspiel von Kollagen und Proteoglykanen.

Abstract

Purpose

Keratoconus is a non-inflammatory disease characterized by progressive thinnning of the central cornea. There are indications for an autosomal dominant heredity. Our purpose was to find correlations between gene expression and structural changes in extracellular matrix components.

Methods

Stromal RNA (keratoconus and comparison) was isolated from corneas, transformed to cRNA and analysed using biochips (Affymetrix). Structural investigations were performed by laser scanning and transmission electron microscopy.

Results

In keratoconus corneas there was an upregulation of different extracellular matrix components (collagen XV, metalloproteases) and a down-regulation of collagen IV (α1, α3) and versican. The morphological changes correlated to genetic obtained data. The orthogonal arrangement of the collagen fibrills (anteriorly and central) was altered in the collagen matrix of keratoconus corneas.

Conclusions

The changes point on deregulation of the matrix arrangement. The interest in the cause of the disease is focused on the interfibrillar arrangement, the interaction between collagen and proteoglucanes.

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Danksagung

Die Autoren danken Prof. Dr. rer. nat. Stave (Universität Rostock), Prof. Dr. rer. nat. L. Jonas (Universität Rostock), Dr. rer. nat. J. Berlau (Universität Jena) und Dr. rer. nat. G. Holzhüter (Universität Rostock) für ihre hilfreiche Unterstützung.

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Authors and Affiliations

  1. Augenklinik, Universität Rostock

    O. Stachs, A. Bochert & R. F. Guthoff

  2. Fachbereich Physik, Universität Rostock

    T. Gerber

  3. Institut für Immunologie, Universität Rostock

    D. Koczan & H. J. Thiessen

  4. Augenklinik der medizinischen Fakultät, Universität Rostock, Doberaner Str. 140, 18055, Rostock

    O. Stachs

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  1. O. Stachs
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  2. A. Bochert
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  3. T. Gerber
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  4. D. Koczan
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  5. H. J. Thiessen
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  6. R. F. Guthoff
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Correspondence to O. Stachs.

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Stachs, O., Bochert, A., Gerber, T. et al. Die Struktur der Extrazellulärmatrix bei Keratokonus. Ophthalmologe 101, 384–389 (2004). https://doi.org/10.1007/s00347-003-0902-3

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