Some proteinase and growth factor genes (e.g.,
cathepsin F and
HGF) were upregulated in diabetic and DR corneas, but a number of them (including several MMPs) showed decreased expression compared with normal corneas (
Fig. 1 ;
Table 3 ).
Table 3lists these genes, some of which were selected for further analysis. Of the tissue inhibitors of metalloproteinase
(TIMP) genes, only
TIMP-4, which was recently found in the cornea,
37 was differentially decreased in DR corneas; the other TIMPs were unchanged (
Table 3 ; Ref.
24 ). A member of the cathepsin family of cysteine proteinases,
38 cathepsin F was upregulated in DR corneas and was studied in more detail. The same was true for HGF
(Table 3) , important for cell migration and wound healing.
39 40 Although it was a little less than twofold higher in DR corneas, its change was statistically significant and it was thus selected for further analysis. Because HGF signals through its tyrosine kinase receptor, c-met,
41 42 its post–microarray analysis was also carried out even though it was decreased less than twofold. Another potent cell migration mediator, thymosin β
4 (X-linked),
43 44 45 was downregulated in DR corneas and was also evaluated further. A similar decrease was observed for one member of fibroblast growth factor (FGF) family, FGF-3/Int-2 (
Fig. 1 ;
Table 3 ). It was selected for further analysis because of its importance for corneal epithelial cell differentiation
46 and the fact that one of its receptors, FGFR3, was concomitantly downregulated. A marked increase in diabetic corneas of recently described interleukin (IL)-27 was not further verified because of the lack of antibodies reacting with human tissues. Many other interleukins and their receptors were downregulated in diabetic corneas
(Fig. 1) . A decreased expression for
laminin α4 gene was observed in DR corneas
(Table 3) . This chain has not been documented in cornea before, and it was of interest to identify its distribution patterns.