1Berlau J., 2Koczan D., 3Seitz B., 2Thiesen H. J., 1Guthoff R. F.

1Institut für Ernährungswissenschaften, Lehrstuhl für Ernährungs-toxokologie, Friedrich-Schiller Universität Jena; 3Universitätsaugenklinik Erlangen; 2Institut für Immunologie, Rostock

Introduction: Keratoconus is an ocular non-inflammatory disease characterised by progressive thinning and scarring of the central cornea which becomes conical and thin, eventually resulting in visual impairment. The exact cause of the disease remains unclear. Clinical studies provide strong indications of a major role for genes in its aetiology. We examined the involvement in the manifestation of keratoconus of 5,600 known genes. Special attention was given to the up or down regulation of the so far described components possibly involved in keratoconus.
Methods: Two corneas were compared, one from a patient with keratoconus and one with a lagochoroidal melanoma. Specimens were placed in GTC lysisbuffer (Qiagen, Hilden, Germany), the tissue was disrupted with a FastPrep™ machine (Savant), followed by the spin column protocol of the RNeasy™ Kit (Qiagen) was performed. Synthesis of cDNA, production of biotin-labelled cRNA and hybridisation procedures were performed according to the manufacturer's recommendations. Results were analysed using GeneChip 3.1 Analysis Suite software.
Results: In keratoconus we found an upregulation of collagens I, V and VI, connexin43, serum amyloid A, SRP1-like protein, small proline-rich protein II (sprII), metalloproteases, fibronectin, desmocollins and desmogleins. A downregulation was observed for TIGR protein, cytokeratin 15, keratin 19 and eyes absent homologue (Eab1). In the keratoconus cornea we found changed mRNA levels for only some of the gene products described by other authors.
Conclusion: These findings might be specific for keratoconus. Connexin 34, sprII and the described collagens may have a role in the interconnection of fibroblasts, cross-bridging and fibril assembly in wound healing processes, whereas matrix metalloproteinases, SRP1 and the downregulation of keratins contribute to degradation and remodeling of corneal tissue. Our results indicate that keratoconus is a process in which both repairing and degrading mechanisms operate at the same time.

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