Phenotypic Investigation of Cell Junction–Related Proteins in Gelatinous Drop-Like Corneal Dystrophy

Abstract

This is the first demonstration of the unique expression patterns of the major cell-junction-related proteins in GDLD corneas. The results show that in corneas with the Q118X mutation, there is a disturbance in cell-to-cell and cell-to-substrate junctions. These findings are an important step toward elucidating the pathogenesis of GDLD.

Clinical staining of the ocular surface: Mechanisms and interpretations

“…This is associated with an absent expression of ZO-1 and occludin in the tight junctional region of the superficial cells and a deficiency of claudin À1 and of desmoplakin in surface cells (Takaoka et al, 2007). These changes could explain the permeability change, but other, unknown defects, could also contribute and have not been excluded.…”

Gelatinous drop-like corneal dystrophy: a review

“…The gene mutation and the disturbed localisation of cell-to-cell adhesion molecules cause an abnormal increase in corneal epithelial permeability 35. In addition, the phosphatidylinositol 4,5-bisphosphonate (PIP 2 ) binding site, presumed to be located at the C-terminal intracellular domain of TACSTD2 gene, has an ability to regulate binding to other molecules or the plasma membrane.…”

“…In addition, the phosphatidylinositol 4,5-bisphosphonate (PIP 2 ) binding site, presumed to be located at the C-terminal intracellular domain of TACSTD2 gene, has an ability to regulate binding to other molecules or the plasma membrane. The mutations may lead to loss of the PIP 2 binding site, thereby leading to loss of the various cell adhesion functions 35. To summarise, TACSTD2 is an important component of desmosomes and zonulae occludentes and is central to disease pathogenesis in GDLD.…”

The Genetics and Pathophysiology of IC3D Category 1 Corneal Dystrophies

“…25 Important cell-junction proteins, including occludin, tight junction protein 1, and claudins (1, 4, and 7), are absent or reduced in the cell junctions in GDLD corneas. 25,26 The basement membrane integrins are also mislocalized. 25 Gelatinous masses of amyloid deposits have been attributed to the increased barrier permeability of the corneal epithelium in the absence of TACSTD2, leading to the penetration and accumulation of the globular protein lactoferrin from ocular secretions (Fig.…”

“…26 It is possible that lactoferrin has additional roles in GDLD, as it has also been detected in the nuclei of epithelial cells in patients with GDLD. 26 Gelatinous drop-like corneal dystrophy is a rare disease that is most prevalent in the Japanese population, where a p.Gln118X founder mutation in TACSTD2 has been described. 27 The p.Gln118X mutation in the thyroglobulin repeat domain leads to a truncated protein that lacks the transmembrane domain.…”