Enigma of the Abundant Water-Soluble Cytoplasmic Proteins of the Cornea

Abstract

It is accepted that the taxon-specific, multifunctional crystallins (small heat-shock proteins and enzymes) serve structural roles contributing to the transparent and refractive properties of the lens. The transparent cornea also accumulates unexpectedly high proportions of taxon-specific, multifunctional proteins particularly, but not only, in the epithelium. For example, aldehyde dehydrogenase 3 (ALDH3) is the main water-soluble protein in corneal epithelial cells of most mammals (but ALDH1 predominates in the rabbit), whereas gelsolin predominates in the zebrafish corneal epithelium. Moreover, some invertebrates (e.g., squid and scallop) accumulate proteins in their corneas that are similar to their lens crystallins. Pax-6, among other transcription factors, is implicated in development and tissue-specific gene expression of the lens and cornea. Environmental factors appear to influence gene expression in the cornea, but not the lens. Although no direct proof exists, the diverse, abundant corneal proteins may have evolved a crystallinlike 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 common function.

Early lens development in the zebrafish: A three‐dimensional time‐lapse analysis

“…To date, genetic and molecular approaches have been at a loss to define the mechanisms regulating the dynamic variations in the differentiation that account for the structural specializations and symmetry of the transparent and refractile lens cell structure. Currently, the refracton hypothesis is the singular theory addressing the molecular genetics for transparency and refractive power of biological optics (Piatigorsky, 2001(Piatigorsky, , 2008. The cornerstone of the refracton hypothesis is that the lens and cornea accumulated diverse, taxonspecific multifunctional proteins by a gene sharing strategy, which contributed to the optical properties of both tissues.…”

Mechanistic Implications of the Cysteine−Nicotinamide Adduct in Aldehyde Dehydrogenase Based on Quantum Mechanical/Molecular Mechanical Simulations

“…Should the adduct also exist in ALDH3, covalent binding of NAD to the enzyme could provide a basis for enhancing the ability of ALDH3 to provide direct UV protection to the eye, as has been considered (48,49), or to maintain an added defense against products UV-induced lipid peroxidation (in addition to 4-hydroxynonenal) which could be directly deleterious to the thiol. At the moment, this remains conjecture, since no evidence has been found to suggest adduct formation in ALDH3.…”

Myofibroblast Differentiation Modulates Keratocyte Crystallin Protein Expression, Concentration, and Cellular Light Scattering

“…19 -22 Since the expression of these proteins is similar to that of the lens, both in abundance and taxon specificity, it has been suggested that corneal crystallins play a role in determining the transparent and refractive properties of the cornea through a metabolic or structural function. 23 In support of this hypothesis, expression of corneal crystallins has been shown to be environmentally and developmentally regulated with a marked increase in expression after eyelid opening, exposure to light, and development of corneal transparency. 24,25 From the…”