Overexpression of matrix metalloproteinase-10 and matrix metalloproteinase-3 in human diabetic corneas - A possible mechanism of basement membrane and integrin alterations

We have previously described decreased immunostaining of nidogen-1/entactin ; laminin chains alpha1, alpha5, beta1,gamma1; and epithelial integrin alph a (3)beta (1) in human diabetic retinopathy (DR) corneas, Here, using 142 h uman corneas, we tested whether these alterations might be caused by decrea sed gene expression levels or increased degradation, By semiquantitative re verse transcription-polymerase chain reaction, gene expression levels of th e alpha1, alpha5, and beta1 laminin chains; nidogen-1/entactin; integrin al pha (3) and beta (1) chains in diabetic and DR corneal epithelium were simi lar to normal. Thus, the observed basement membrane and integrin changes we re unlikely to occur because of a decreased synthesis. mRNA levels of matri x metallo-proteinase-10 (MMP-10/stromelysin-2) were significantly elevated in DR corneal epithelium and stroma, and of MMP-3/stromelysin-1, in DR corn eal stroma, No such elevation was seen in keratoconus corneas, These data w ere confirmed by immunostaining, zymography, and Western blotting. mRNA lev els of five other proteinases and of three tissue inhibitors of MMPs were s imilar to normal in diabetic and DR corneal epithelium and stroma, The data suggest that alterations of laminins, nidogen-1/entactin, and epithelial i ntegrin in DR corneas may occur because of an increased proteolytic degrada tion. MMP-10 overexpressed in the diabetic corneal epithelium seems to be t he major contributor to the observed changes in DR corneas, Such alteration s may bring about epithelial adhesive abnormalities clinically seen in diab etic corneas.