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Purpose: To describe a severe phenotype of Meesmann's epithelial corneal dystrophy (MECD) and to determine the underlying molecular cause., Methods: We identified a 30-member family affected by MECD and examined 11 of the 14 affected individuals. Excised corneal tissue from one affected individual was examined histologically. We used PCR and direct sequencing to identify mutation of the coding regions of the KRT3 and KRT12 genes., Results: Cases had an unusually severe phenotype with large numbers of intraepithelial cysts present from infancy and they developed subepithelial fibrosis in the second to third decade. In some individuals, the cornea became superficially vascularized, a change accompanied by the loss of clinically obvious epithelial cysts. Visual loss from amblyopia or corneal opacity was common and four individuals were visually impaired (≤6/24 bilaterally) and one was blind (<6/60 bilaterally). In all affected family members, there was a heterozygous missense mutation c. 395T>C (p. L132P) in exon 1 of the KRT12 gene, which codes for the helix-initiation motif of the K12 polypeptide. This sequence change was not found in unaffected family members or in 100 unaffected controls., Conclusions: The Leu132Pro missense mutation is within the helix-initiation motif of the keratin and is predicted to result in a significant structural change of the K12 protein. The clinical effects are markedly more severe than the phenotype usually associated with the Arg135Thr mutation within this motif, most frequently seen in European patients with MECD.

The fibroblast is the central player in the wound repair and scarring processes that occur in the anterior segment of the eye. Glaucoma filtration surgery is the ultimate example of the importance of the wound healing process, as this process is the major determinant of the success of this procedure. We highlight the role of the fibroblast, and discuss some of the growth factors stimulating fibroblast proliferation, migration and extracellular matrix production in the wound environment. We also review current methods of suppressing fibroblast proliferation, the new concepts that have arisen from laboratory studies, and future directions of investigation and treatment.

An overview is presented of the retinal pigment epithelium (RPE) cell in repair and regeneration. Changes in the RPE associated with repair activities have been described as metaplasia. However, evidence is presented to show that RPE cells do not become either fibroblasts or macrophages but merely adopt the appearance of these cell types in pathological conditions. The phenotypic alterations seem to be substrate-related. The fibroblast form predominates on two-dimensional substrates rich in fibronectin and in three-dimensional collagen matrices. The macrophage form seems to be associated with insubstantial or inadequate substrates such as the vitreous, photoreceptor debris and some cell surfaces. In altered circumstances the dedifferentiated RPE can rapidly revert to an epithelioid form. However, the regeneration of an effective RPE mosaic is more difficult and dependent on many factors including the size of the initial lesion, the condition of the basement area, the status of the neuroretina and the existing pathology in the eye. The importance for the regeneration of a normal functioning RPE of the cells being out of the cell cycle, establishing effective junctioning, reorganising their cytoskeleton and having the required adhesive balance with the basement membrane is emphasised.

We compared the distribution of the adhesive extracellular matrix glycoproteins thrombospondin and cellular fibronectin in epiretinal membranes. A total of nine membranes were investigated with immunohistochemical techniques. Thrombospondin and cellular fibronectin immunoreactivity were observed in seven of the specimens and immunostaining for the two glycoproteins was co-localised in four of the membranes. The findings indicate that thrombospondin contributes to the extracellular glycoprotein content of epiretinal membranes and is frequently co-distributed with cellular fibronectin in the tissue. As a consequence, thrombospondin may play a role in the assembly of the extracellular matrix of epiretinal membranes.