Congenital stromal corneal dystrophy and decorin

Eyvind Rødahl

Dept. of Ophthalmology, Haukeland University Hospital, N-5021 Bergen, Norway.

Congenital stromal corneal dystrophy (CSCD) is a rare autosomal dominant disorder characterized by corneal clouding due to the presence of fine stromal opacities seen as small flakes and spots. We have recently studied a large Norwegian family with this disorder. Most had visual acuity within the range of 0.63-0.3. Four out of 11 had strabismus. Pachymetry revealed increased thickness of the cornea. Penetrating keratoplasty was performed in 18 out of 22 eyes at a mean age of 20 years. The grafts remained clear in 56% of the eyes and in an additional 33% only minimal opacities were seen.

Transmission electron microscopy of CSCD corneas showed appearently normal lamellae of collagen fibrils separated by abnormal layers of an amorphous substance with thin, randomly arranged filaments. Keratocytes were located in the vicinity of these layers.

Molecular genetic analysis including a genome wide screening with microsatellite markers revealed a c.967delT mutation in the decorin gene. Later, we found a c.941delC mutation in DCN in a Belgian family. The two frame-shift mutations are predicted to result in the introduction of the same stop-codon causing the expression of a decorin protein that is lacking the 33 C-terminal amino acids.

We now report on the expression of decorin in CSCD corneas and keratocyte cultures, and in HEK293 cells transfected with plasmids containing either wild type or mutant (c.967delT) DCN. Decorin mRNA was assayed using Q-RT-PCR, and the protein was detected by immunoblot analysis. Recombinant decorin was analyzed by gelfiltration. Corneal biopsies were examined by cuprolinic blue staining and immunoelectronmicroscopy. Data from these studies will be presented.