The Role of the Extracellular Matrix in TGFBI-Related Corneal Dystrophy Development

The transparent nature of the cornea makes it unique among tissues in the human body. The distinct composition of the corneal proteome appears to be a key factor in protein aggregation caused by mutations in the gene encoding transforming growth factor beta-induced protein (TGFBIp). This chapter reviews the current understanding of the biophysical and biochemical properties of corneal TGFBIp carrying one of the more than 70 known disease-causing mutations. Notably, TGFBIp exhibits a dual aggregation propensity, leading to either amorphous or amyloid insoluble protein aggregates in the cornea upon mutation. Emerging research utilizing protein characterization techniques such as mass spectrometry and X-ray crystallography suggests that the proteolytic machinery in the cornea plays a central role in driving TGFBIp aggregation.