Early recurrence of Groenouw type I corneal dystrophy after phototherapeutic keratectomy. Molecular biology study suggests epithelial genesis]

Granular corneal dystrophy Groenouw type 1 (GGI) is a rare autosomal dominant disease caused by allelic mutations of the BIGH3 gene. The specific phenotype is characterized by granular opacities (white, sharply demarcated spots resembling bread crumbs) in corneal stroma, which cause recurrent corneal erosions and blurred vision. Phototherapeutic keratectomy (PTK) is an effective procedure that improves visual acuity, but recurrences are unavoidable. Though GGI deposits are well described, their origin is not completely known. The production of mutated keratoepithelin protein (a product of the BIGH3 gene) is the first step necessary for deposits to appear. Molecular biology experiments were conducted to determine the role of corneal cell types in the genesis of early recurrent deposits of post-PTK GGI.Tissue specimens from a patient undergoing penetrating keratoplasty for recurrence of GGI (12 months after PTK) and five normal corneas were examined by hybridization in situ and immunohistology to study the expression of BIGH3 and location of keratoepithelin.Only one healthy cornea expressed BIGH3 mainly in the epithelium and less in keratinocytes and endothelial cells. In the GGI corneas, BIGH3 was highly expressed in the modified, hyperplastic epithelium. The keratoepithelin was accumulated under the epithelium where deposits were formed.This observation confirms that corneal epithelium is the main producer of mutated keratoepithelin on the cellular scale and thus constitutes the principal source of dystrophic deposit formation during recurrence.