Enigma of the abundant water-soluble cytoplasmic proteins of the cornea - The "refracton" hypothesis

It is accepted that the taxon-specific, multifunctional crystallins. (small heat-shock proteins and enzymes) serve structural roles contributing to th e transparent and refractive properties of the lens. The transparent cornea also accumulates unexpectedly high proportions of taxon-specific, multifun ctional proteins particularly, but not only, in the epithelium. For example , aldehyde dehydrogenase 3 (ALDH3) is the main water-soluble protein in cor neal epithelial cells of most mammals (but ALDH1 predominates in the rabbit ), whereas gelsolin predominates in the zebrafish corneal epithelium. Moreo ver, some invertebrates (e.g., squid and scallop) accumulate proteins in th eir corneas that are similar to their lens crystallins. Pax-6, among other transcription factors, is implicated in development and tissue-specific gen e expression of the lens and cornea. Environmental factors appear to influe nce gene expression in the cornea, but not the lens. Although no direct pro of exists, the diverse, abundant corneal proteins may have evolved a crysta llinlike role, in addition to their enzymatic or cytoskeletal functions, by a gene sharing mechanism similar to the lens crystallins. Consequently, it is proposed that the cornea and lens be considered as a single refractive unit, called here the "refracton," to emphasize their similarities and comm on function.