Molecular Pathogenesis of Granular Corneal Dystrophy Type 2 (GCD2) and TGFBI-Related Corneal Dystrophies

The transforming growth factor beta-induced gene (TGFBI; BIGH3; βigh3) was first discovered in a human lung adenocarcinoma cell line, where it was upregulated after treatment with the pleiotropic cytokine TGF-β1 (Skonier et al. 1992). TGFBI mRNA encodes a 68-kDa extracellular matrix (ECM) protein, transforming growth factor beta-induced protein (TGFBIp), also described as MP78/70 (Gibson et al. 1997), collagen fiber-associated protein (RGD-CAP) (Hashimoto et al. 1997), BIGH3, βigh3, or kerato-epithelin (Munier et al. 1997; Han et al. 2016). TGFBIp consists of an N-terminal 23 residues of secretory signal peptide sequence, a cysteine-rich EMI domain, four homologous fasciclin 1 (FAS1) domains which each contain 140 amino acid residues at the N-terminus, and an arginine-glycine-aspartate (RGD) motif which binds to integrin at the C-terminus (Han et al. 2016). In this chapter, pathophysiology of normal and mutated TGFBIp is described in detail.