Corneal epithelial tight junction proteins and membrane sulfhydryl groups

The corneal epithelial membrane sulfhydryl groups and tight junction proteins collectively constitute the primary physiological barrier of the ocular surface, regulating the entry of substances into the eye (Saghizadeh et al., 2020; Yi et al., 2000). Tight junction proteins, including Zonula occludens-1 (ZO-1), occludin, and various claudins, seal the intercellular spaces between superficial epithelial cells, restricting paracellular transport (Sekijima et al., 2013; Yi et al., 2000). Membrane-associated sulfhydryl (thiol) groups, found on mucus glycoproteins and surface proteins like keratins, provide sites for covalent interaction with thiolated polymers, also known as thiomers (Bernkop-Schnürch, 2005; PharmaExcipients, 2023). In pharmacological applications, these structures are targeted to enhance the bioavailability of topically applied drugs (Gote et al., 2019; Irimia et al., 2018). Thiomers form disulfide bonds with the sulfhydryl groups to increase mucoadhesion and residence time, while also triggering the reversible opening of tight junctions to facilitate the delivery of hydrophilic molecules (Bernkop-Schnürch, 2005; Irimia et al., 2018). While modulating this barrier is essential for treating conditions such as dry eye disease and glaucoma, excessive or irreversible disruption can lead to corneal irritation and epithelial toxicity (Gote et al., 2019; Yi et al., 2000).

Other names

Corneal epithelial barrierOcular surface barrierCorneal tight junctionsThiol-rich corneal membrane proteins

Mucoadhesion via disulfide bond formation with membrane sulfhydryl groups and reversible opening of tight junctions to increase paracellular permeability (Bernkop-Schnürch, 2005; Irimia et al., 2018).