The Genetics and Pathophysiology of IC3D Category 1 Corneal Dystrophies

Abstract

Corneal dystrophies are a group of inherited disorders affecting the cornea, many of which lead to visual impairment. The International Committee for Classification of Corneal Dystrophies has established criteria to clarify the status of the various corneal dystrophies, which include the knowledge of the underlying genetics. In this review, we discuss the International Committee for Classification of Corneal Dystrophies category 1 (second edition) corneal dystrophies, for which a clear genetic link has been established. We highlight the various mechanisms underlying corneal dystrophy pathology, including structural disorganization, instability or maladhesion, aberrant protein stability and deposition, abnormal cellular proliferation or apoptosis, and dysfunction of normal enzymatic processes. Understanding these genetic mechanisms is essential for designing targets for therapeutic intervention, especially in the age of gene therapy and gene editing.

Raman Spectroscopic Study of Amyloid Deposits in Gelatinous Drop-like Corneal Dystrophy

“…GDCD was linked to mutations in the tumor-associated calcium signal transducer 2 ( TACSTD2 ) gene, which encodes for TACSTD2, a human transmembrane glycoprotein, essential for the integrity of the corneal epithelial barrier [ 9 ]. In GDCD, the dysfunction of TACSTD2 interferes with tight junction proteins claudin-1 and -7, causing the penetration of lactoferrin, lysozyme, and other molecules from the tears and their deposition as amyloid deposits in the stroma [ 10 , 11 ]. Histologically, acellular deposits able to raise or interrupt the Bowman’s layer were observed in subepithelial and anterior stromal location.…”