More than 60 mutations in
transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic
protein aggregates in the cornea, commonly termed
corneal dystrophies. One mutation, generating an
arginine to
histidine amino acid substitution at position 124 in mature TGFBIp leads to
granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive
protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo
laser-assisted in situ keratomileusis (
LASIK) surgery
protein accumulation is accelerated and they develop massive
protein accumulations a few years after surgery. Here, we present the
protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of
LASIK surgery using LC-MS/MS. Label-free quantification of corneal
extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after
LASIK surgery, which may be important for the
disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of
LASIK surgery when compared to healthy individuals.