In addition to global gene expression analyses, it is also valuable to focus on the significance of individual transcripts
(Table 8) . The highest-expressing cornea-exclusive gene is testican 1. This large secreted multidomain proteoglycan has been shown to have strong inhibitory activity against cathepsin and activation of matrix metalloproteinases (MMPs).
27 28 The corneal epithelium expresses multiple MMPs and cathepsins, in particular, cathepsin L/V2,
29 which in itself shows a high corneal preference
(Table 4A) . Thus, it is intriguing to consider the possibility of a role for testican-1 in locally protecting the corneal epithelial cell surface membrane against the activity of its own proteolytic agents. The third gene in the cornea-exclusive list is a formin isoform. Formins are a conserved family of actin nucleators responsible for the assembly of diverse actin structures such as cytokinetic rings and filopodia. Formin binding to the barbed end of actin filaments increases filament flexibility and has been documented to cause critical modulation of cell adhesion and cell motility. The exclusive presence of a certain formin isoform in the corneal epithelium is likely to play a weighty role in the phenotypic difference of this tissue with that of its ocular surface counterpart. It will be interesting to assess formin’s contribution to the rapid migration in corneal wound healing and response to physical pressure.
30 Another intriguing and unexpected corneal gene is cartilage acidic protein 1 (CRTAC1;
Table 4A ), a matrix component with high affinity for integrins. It is profusely expressed in cartilage, a mostly avascular tissue, but it is absent in most other organs and tissues examined, including brain, liver, and muscle.
31 Its corneal expression may indicate that its function is somehow related to the avascular environs. Adiponectin, is another cornea-preferred, highly expressed gene. In a fashion similar to CRTAC1, it codes for a protein that until now has been believed to be specific for one cell type, the adipocyte.
32 Adiponectin is a secreted protein with multiple systemic functions including growth-promoting activity in epithelial cells.
33 34 If indeed, adiponectin is secreted by the corneal epithelium, it may function as part of the proliferation promoter autocrine loop. Other valuable corneal preferred genes to be considered for future investigations are chemokine CXCL14 (BRAK) and Dickkoft 3 (DKK3). CXCL14 plays a central role in monocyte attraction and their in situ conversion to Langerhans cells.
35 Thus, it could be important for the ontogeny of these immunosurveillance cells in the limbus. DKK proteins are involved in the regulation of the WNT-β-catenin cascade, which, in turn may control developmental cell fate
36 and the expression of connexin43, another highly expressed corneal preferred transcript
(Table 4A) . DKK2, which is not expressed in the mature human cornea
(Table 9) , has recently been found to be a critical component of corneal epithelial development in mouse.
37 Thus, it is possible that in humans, this role is performed by DKK3.