Corneal dystrophies in the light of modern molecular genetic research

Abstract

Modern methods of molecular genetics have resulted in new insights into the pathogenesis of corneal dystrophies which now require a new classification. Clinical evidence, the results of histopathological and electron-microscopical examinations, especially in cases of recurrence which reflect early disease, and the immunohistochemical analysis of the deposits have already aroused the suspicion that the "old" classification dividing the dystrophies into those of the epithelium, of the so-called anterior membrane, of the stroma and of the endothelium may no longer be adequate. The detection of the BIGH 3 gene which is mainly expressed in the corneal epithelium, and its gene product keratoepithelin, have led to the insight that the so-called anterior membrane dystrophies (Reis-Bücklers, Thiel-Behnke) as well as the more common "classical" stromal dystrophies (granular dystrophies Types I and II, lattice dystrophies Types I and IIIA) are caused by different mutations of the above mentioned BIGH3 gene and are thus to be regarded as epithelial in origin. Lattice dystrophy Type II is part of the Meretoja syndrome, a systemic amyloidosis, and is caused by a mutation of the gelsoline gene on chromosome 9 (9q34). Gelsoline is also predominantly expressed in the corneal epithelium. In addition, the responsible genes, their gene-products and the mutations are known for Meesmann's epithelial dystrophy and for the so-called gelatinous drop-like dystrophy, while in other dystrophies only the location on a certain chromosome can be given, namely: 16q22 for the macular dystrophy, 1p36 for the central crystalline dystrophy of Schnyder and 20p11.2-q11.2 for the congenital hereditary endothelial and for Schlichting's posterior polymorphous dystrophies. As the production rate of new results in molecular genetics is very fast, the proposed new classification can only be of preliminary character.